International Journal of Current Research and Review
ISSN: 2231-2196 (Print)ISSN: 0975-5241 (Online)
logo
slider
slider
slider
slider
Bootstrap Slider

Indexed and Abstracted in: Crossref, CAS Abstracts, Publons, Google Scholar, Open J-Gate, ROAD, Indian Citation Index (ICI), ResearchGATE, Ulrich's Periodicals Directory, WorldCat (World's largest network of library content and services)

Search Articles

Track manuscript

Full Html

IJCRR - 3(5), May, 2011

Pages: 56-63

Print Article   Download XML  Download PDF

PHENOTYPING - AN OVERVIEW

Author: Kavita Atre, Rahul Mayee, Sanjay Toshniwal

Category: Healthcare

Abstract:The medicinal sciences have always aimed at an increased effort to increase the patient safety and reduce medical errors. These errors are mainly caused due to therapeutic failure and adverse drug
reactions which arise as a result of incorrect dosing of the routinely prescribed drugs. The drugs
are metabolized by drug metabolizing enzymes of which the Cytochrome P450 enzyme forms a
major class. It is now being observed that with the descriptions of genetic polymorphism in the
drug metabolizing enzymes, the field of pharmacogenetics may improve medical care through a
reduction in adverse drug reactions oriented errors. The status of these drug metabolizing
enzymes can be characterized using phenotyping studies which categorizes the population into
poor, extensive or ultra-extensive metabolizers. Such a division of population based on their
metabolic status will be of immense help to the medical authorities in deciding the drug dose.
This paper reviews the field of Cytochrome P450 (CYP) genetics and explores factors that impact
the utility of this information in clinical practice to avoid incidences occurring due to incorrect
metabolism of the routinely prescribed drugs.

Keywords: Phenotyping, Cytochrome P450, Drug metabolism

Full Text:

INTRODUCTION

The two areas that significantly represent patient‘s safety concern are – therapeutic failure and adverse drug events (ADEs). [1] Therapeutic failure refers to lack of efficacy due to lack of dosing where as ADEs include both compliance issues and medical dispensing errors. [2] On the other hand, adverse drug reactions (ADRs) are the complications that occur despite appropriate dispensing of the correct medication at the ?intended dose?. The ADEs are usually caused when there is presence of excess drug in the body for a time longer than is necessary. The drug outcome is mostly based upon the genetic make-up of an individual which is likely to exhibit inter-individual difference in population owing to ?genetic polymorphism?. [3] Hence, the intended dose might not prove appropriate for every individual.

Studying polymorphic drug metabolism in a population helps to categorize individuals based on their ability to metabolize routinely prescribed drugs. Such studies are referred to as ?phenotyping studies? and they are carried out by using an appropriate drug as a substrate for the respective enzymes and determining the drug-metabolite ratio. Based on this ratio the population is categorized into poor, extensive or ultra-extensive metabolizers. These phenotyping studies would be an immense help to medical and therapeutic sciences to have prospective access to genetic information that might predict efficacy and/or toxicity of an individual for respective drugs.

Drug metabolism and Cytochrome P450 (CYP) Enzyme System: Drugs are almost all xenobiotics. Drug metabolism is metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. Drug metabolizing enzymes (DMEs) often convert lipophilic chemical compounds into more readily excreted polar products. This drug metabolism can result in toxication or detoxication – the activation or deactivation of the chemical. Drug metabolism is typically classified as Phase I and Phase II reactions. Phase I reactions are biotransformation reactions that alter the structure of the parent drug converting it to subsequent metabolites. Phase II reactions are usually known as conjugation reactions and they modify the drug covalently making it less toxic to body. Both Phase I and Phase II DMEs can impact a drug‘s activity.

Phase I DMEs include esterases, dehydrogenases, flavin monooxygenases and the Cytochrome P450 (CYPs). [4] Cytochrome P450 (CYP450) enzymes are essential for the production of cholesterol, steroids, prostacyclins, and thromboxane A2 and are located in the membranes of the smooth endoplasmic reticulum. They also are necessary for the detoxification of foreign chemicals and the metabolism of drugs. CYP450 enzymes are so named because they are bound to membranes within a cell (cyto) and contain a heme pigment (chrome and P) that absorbs light at a wavelength of 450 nm when exposed to carbon monoxide. There are more than 50 CYP450 enzymes, but the CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 enzymes metabolize 90 percent of drugs. [5, 6] out of these six enzymes, CYP2D6 and CYP3A4 is found to have maximum activity of 40% and 20% respectively [7] These enzymes are predominantly expressed in the liver, but they also occur in the small intestine (reducing drug bioavailability), lungs, placenta, and kidneys. [6]

Genetic Polymorphism and Cytochrome P450: Genetic Polymorphism is defined as the inheritance of a trait controlled by a single genetic locus with two alleles , in which the least common allele has a frequency of about 1% or greater. [7] One of the most extensively studied genetic polymorphism is the polymorphism observed in drug metabolizing enzymes. These changes in gene expression accompany drugmetabolizing enzyme gene polymorphism and cause alteration in enzymatic activity showing a gene-dosage effect. Genetic polymorphism has been found to categorize people into three different types of phenotypes based on their extent or capability to metabolize a drug. Normal population is usually an extensive metabolizer (EM); poor metabolizers (PM) show accumulation of the specific drug substance hinting at the deletion of or mutation in both alleles for phenotypic expression whereas ultra extensive metabolizers (UEM) exhibit an increased drug metabolism which is an autosomal dominant trait arising from gene amplification. [8] A specific gene encodes each CYP450 enzyme. Every person inherits one genetic allele from each parent. Alleles are referred to as ?wild type? or ?variant,? with wild type occurring most commonly in the general population. An ?extensive? (i.e., normal) metabolizer has received two copies of wild-type alleles. Polymorphism occurs when a variant allele replaces one or both wild-type alleles. Variant alleles usually encode a CYP450 enzyme that has reduced or no activity. [9] Persons with two copies of variant alleles are ?poor? metabolizers, whereas those with one wild-type and one variant allele have reduced enzyme activity. Finally, some persons inherit multiple copies of wild-type alleles, which results in excess enzyme activity. This phenotype is termed an ?ultra extensive? metabolizer. [10]

 

CYP450 enzyme polymorphism is responsible for observed variations in drug response among patients of differing ethnic origins. [10, 11, 12] For example, 7 percent of white persons and 2 to 7 percent of black persons are poor metabolizers of drugs dependent on CYP2D6, which metabolizes many beta blockers, antidepressants, and opioids. [13, 14] One in five Asian persons is a poor metabolizer of drugs dependent on CYP2C19, which metabolizes phenytoin (Dilantin), phenobarbital, omeprazole (Prilosec), and other drugs. [15] Variance in drug response among persons of different ethnic origins also can be caused by genetic variations in other drug-metabolizing enzymes, drug transporters, and drug receptors. [16] The understanding of gene dosage effect related to the function changes of genetic polymorphisms of drug metabolizing enzymes, transporters and receptors not only provide potential novel insight into the effect of genetic polymorphisms on drug efficacy and toxicity but also point to the potential role of it in genotype directed tabloid drug therapy. Even though the additional larger and controlled studies are needed to justify changes of treatment strategies, the pharmacogenetics approach to individualize therapy in some patients is promising.

Phenotyping: Phenotyping is one of the most common methods used to study genetic polymorphism. It requires intake of a probe drug; the metabolism of which is known to be solely dependent on one of the Cytochrome P450 (CYP) enzymes such as CYP2D6, CYP3A4 etc. The excretion of parent compound and/or metabolite in urine is used to calculate the metabolic ratio, which is the measure of individual‘ respective enzyme activity. [18, 19] Phenotyping studies can also be carried out by analyzing blood or saliva samples. [20, 21] This phenotyping study divides the population as per their genetic polymorphism into poor, extensive or ultra extensive metabolizers and thus can be used in deciding the drug dose for each individual. Defining the individual‘s phenotype, relative to a reference substrate, allows the drug metabolism phenotype for other substrates of that enzyme to be predicted easily. [22]

Significance of phenotyping studies: The clinical importance of various CYPs and their genetic polymorphisms has paved way for a new fields- ?Pharmacogenetics? and ?Pharmacogenomics?. The traditional pharmacogenetic approach relies on studying sequence variations in candidate genes suspected of affecting drug response. On the other hand, pharmacogenomic studies encompass the sum of all genes, i.e., the genome. Thus, it can be said that pharmacogenomics has evolved from the academic science, pharmacogenetics, which focused primarily on genetic polymorphisms in DMEs. The "one drug fits all" approach of the Pharma industry could, with the fruits of pharmacogenomic research, evolve into an individualized approach to therapy where optimally effective drugs are matched to a patient's unique genetic profile. [23]

Standard drug doses may cause adverse effects related to elevated drug serum levels if a person is a poor metabolizer or has a CYP450 enzyme inhibitor added to therapy. [24, 25] Adverse effects are more likely to occur if a drug has a narrow safety range or is dependent on only one enzyme for metabolism. This can be best explained by the following illustrations.

Illustration 1: A 35-year-old white woman with panic disorder was treated with paroxetine (Paxil). She developed unrelated hypertension, for which the physician prescribed 50 mg daily of extended-release metoprolol (Toprol XL). The patient became symptomatically orthostatic after a few days and presented to the emergency department. In this example, metoprolol, which is metabolized solely by CYP2D6, was present in higher serum levels in the patient because of the use of paroxetine.

Peak serum levels of simvastatin (Zocor), which is metabolized solely by CYP3A4, also can increase by many times in patients who are poor metabolizers or with the addition of a potent inhibitor, increasing the risk of myopathy and rhabdomyolysis at usual doses. [26]

Illustration 2: The linkage between the HER2/neu oncogene and the efficacy of Herceptin® for the treatment of advanced breast cancer is another example where pharmacogenomics has proven successful. Profiling of subjects with breast tumours expressing HER2/neu (class 2-3 HER2/neu immunohistochemitsry staining) was utilised to compare clinical efficacy in late stage drug development with those individuals most likely to respond to therapy. [27] The linkage between HER2/neu levels assessed by a diagnostic test and selection of therapy with Herceptin® is one of the first pharmacogenomic applications approved by the FDA. [28] This is also an excellent example demonstrating that each patient (and his disease) is highly variable, requiring treatment based on the expression of tumour genes. Only 25 - 30% of all breast cancers overexpress HER2/neu, effectively segmenting the market for Herceptin®. However, physician and patient confidence in selecting this therapy based on a prospective pharmacogenomic approach will actually result in better disease management and compliance.

Ultimately, this approach will mean that positioning and differentiation of drug treatment will allow drugs that would otherwise not be approved to be used in a select population of patients, with premium pricing and better acceptance. [28]

Methodologies used in phenotyping: Probe substrates (or probe drugs) are compounds that are predominately or exclusively metabolized in vitro by an individual CYP enzyme. [29] The metabolism of the candidate probe is generally characterized through the use of preparations containing individually expressed human CYP enzymes or preparations of human liver microsomes. [30] Drugs that are selectively metabolized and that can be safely administered to humans may be used as in vivo probe drugs for the purposes of phenotyping i.e., estimating CYP enzyme activity.

1) Single drug probes- The phenotyping procedure typically involves the administration of the probe drug and the collection of blood and/or urine in order to determine some measure of the enzyme‘s functional activity. Typically, as small a dose of the probe drug as possible is administered so as to avoid or minimize undesirable clinical effects. An index of enzyme activity, also referred to as a phenotypic trait measure, is chosen to reflect the catalytic activity of a single pathway of metabolism. The intrinsic clearance of a probe or of the metabolite(s) produced, termed formation clearance, is the most appropriate measure of enzyme activity. [31]

2) Cocktail method- Administering multiple probe compounds concomitantly, termed the ?cocktail? strategy, is a useful method in the assessment of drug-metabolizing enzyme activities because it allows for the in vivo assessment of multiple pathways of drug metabolism in a single experiment. [32] The utility of the cocktail strategy, first demonstrated by Schellens and Breimer in multiple investigations, offers several potential advantages in that it reduces participation time for the study subjects and increases efficiency for the investigators by decreasing time and expense. [32] More importantly, this approach minimizes intra-individual variability since the evaluation will occur on one day rather than separate days. Phenotypic data (i.e., enzyme activity) can be obtained simultaneously on multiple pathways while genetic material obtained can be examined for known or novel SNPs in the drugmetabolizing enzyme genes. Thus, the cocktail strategy appears to be an invaluable method to investigate differential modulation of CYP activity. [33]

Current status of phenotyping: Around the world- Several phenotyping studies have been conducted around the globe to determine the phenotype status of an individual. These studies have not only been conducted for different population in various parts of the world but also with respect to different CYP enzymes. Based on these studies different percentages of PM, EM and UEM have been obtained for different enzymes based on the inter-ethnic differences in the population. For example, CYP2C19 the prevalence of PMs has been reported to be 2–5% in Caucasians [34, 35] 4–8

% in Africans [36] and 11–23 % in Orientals. [35]

In Maharashtra: As far as the state of Maharashtra goes, only one such phenotyping study has been conducted in the Mumbai. This study was conducted to study the genetic polymorphism in CYP2C19 enzyme in the Gujrathi and Marwadi population of the Mumbai region. The probe drug used to estimate the enzyme activity was omeprazole (20 mg) whose drug metabolite is 5-hydroxyomeprazole. The DM ratio analyzed on HPLC (High Performance Liquid Chromatography) led to the generation of the phenotyping data. It was seen that 10.36% of this population were poor metabolizers (PM) whereas 89.63% were extensive metabolizers (EM). [36]

 

CONCLUSION

Genetic polymorphism appears to be a significant source of variability observed in the response to drugs. This variability means that information pertaining to interethnic and inter-individual genetic differences can be used to facilitate rational drug discovery and development and to avoid or minimize the incidence of adverse events in clinical trials. Thus, one could generate criteria for selecting patients most likely to benefit from a drug without incurring unnecessary risk. In this review we have seen the clinical application of phenotyping data as they apply to the clinical laboratory as well as to the clinical practitioner. Phenotyping may be indicated in each instance when the therapeutic of choice is a substrate for a polymorphic enzyme. Alternatively, genotyping is indicated when individuals demonstrate suboptimal response to drugs that are substrates for polymorphic enzymes. The advantage of combining phenotyping with therapeutic drug monitoring is that genotyping can predict the PM or UEM drug metabolism phenotypes, and this information can be used in prior dose adjustment or selection of an alternative therapeutic that is not a substrate for the polymorphic enzyme. The cost/healthcare effectiveness of these paradigms has not been extensively studied. Although there would be considerable cost associated with screening all individuals before dosing with these drugs, this cost may be offset by a reduction in costs associated with toxic episodes or therapeutic failure and subsequent intervention.

 

References:

1. Kohn LT, Corrigan JM, Donaldson MS, Eds. To err is human: building a safer health system (Washington). Natl Acad Press. 1999.

2. Institute of Medicine. Crossing a quality chasm: a new health system for twenty first century (Washington). Natl Acad Press. 2001

3. Ingelman-Sundermann M. Genetic polymorphism of CYP450 2D6: clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J.2005; 5:6-13.

4. Ingelman- Sunderberg M. Phamacogenetics of Cytochrome P450 and its applications in drug therapy: the past , present and future. Trends Pharmacol Sci. 2004; 25(4):193-200.

5. Wilkinson GR. Drug metabolism and variability among patients in drug response. N Engl J Med. 2005;352:2211–2221.

6. Slaughter RL, Edwards DJ. Recent advances: the cytochrome P450 enzymes. Ann Pharmacother. 1995;29:619–624. 62 International Journal of Current Research and Review www.ijcrr.com Vol. 03 issue 05 May 2011

7. Evans WE, Relling MV. Pharmacogenimics: translating functional genomics into rational therapeutics. Science. 1999;286:487- 491.

8. Lennard MS. Genetic Polymorphism of sparteine/debrisoquine oxidation: A reappraisal. Pharmacol Toxicol 1990;67:273-283.

9. Nebert DW. Pharmacogenetics: 65 candles on the cake. Pharmacogenetics. 1997;7:435-440.

10. Wilkinson GR. Drug metabolism and variability among patients in drug response. N Engl J Med. 2005;352:2211–2221.

11. Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W. Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. JAMA. 2001;286:2270–2279.

12. Bradford LD. CYP2D6 allele frequency in European caucasians, Asians, Africans, and their descendants. Pharmacogenomics. 2002;3:229–243.

13. Special report: genotyping for cytochrome P450 polymorphisms to determine drug-metabolizer status. Technol Eval Cent Asses Program Exec Summ. 2004;19:1–2

14. Abraham BK, Adithan C. Genetic polymorphism of CYP2D6. Indian J Pharmacol. 2001;33:147–69.

15. Bernard S, Neville KA, Nguyen AT, Flockhart DA. Inter-ethnic differences in genetic polymorphisms of CYP2D6 in the U.S. population: clinical implications. Oncologist. 2006;11:126–135.

16. Chong E, Ensom MH. Pharmacogenetics of the proton pump inhibitors: a systematic review. Pharmacotherapy. 2003;23:460–471.

17. Weinshilboum R. Inheritance and drug response. N Engl J Med. 2003;348:529–537.

18. Linder MW, Prough RA, Valdes R Jr. Pharmacogenetics: a laboratory tool for optimizing therapeutic efficiency. Clin Chem. 1997;43:254-266.

19. Kroemer HK, Eichelbaum M. ?it‘s the genes stupid? molecular basis and clinical consequences of Cytochrome P450 2D6 polymorphism. Life Sci. 1995;56:2285-2298.

20. Hou ZY, Pickle LW, Mayer Sp, Woosley RL. Salivary analysis for determination of dextromethorphan metabolic phenotype. Clin Pharmacol Ther. 1991;49:410-419.

21. Hou ZY, Chen CP, Yang WC, Lai MD, Buchert ET, Chung GM et al. determination of dexromethorphan metabolic phenotype by salivary analysis with a reference to genotype in Chinese patients receiving renal hemodialysis. Clin Pharmacol Ther. 1996;59:411-417.

22. Gonzalez FJ, Skoda RC, Dimura S, Umeno M, Zanger UM, Nebert DW, et al. Characterization of the common genetic defect in humans deficient in debrisoquin metabolism. Nature 1988;331:442–446.

23. Sadee W. Finding the right drug for the right patient.Pharm Res. 1998;15:959- 963.

24. Bradford LD. CYP2D6 allele frequency in European caucasians, Asians, Africans, and their descendants. Pharmacogenomics. 2002;3:229–243.

 25. Meyer UA. Pharmacogenetics and adverse drug reactions. Lancet. 2000;356:1667–1671. 63 International Journal of Current Research and Review www.ijcrr.com Vol. 03 issue 05 May 2011

26. Ballantyne CM, Corsini A, Davidson MH, Holdaas H, Jacobson TA, Leitersdorf E, et al. Risk for myopathy with statin therapy in highrisk patients. Arch Intern Med. 2003;163:553–564.

27. Shak S: Case study: Genetech and the development of Herceptin. Second Annual Pharmacogenomics Event. European Centre for Pharmaceutical Information. 2000.

28. Anderson WH, Fitzgerald CQ, Manasco PK: Current and future applications of pharmacogenomics. New Horizons. 1999;7:262-269.

29. Streetman, D.S., Bertino, J.S., Jr., and Nafziger, A.N. Phenotyping of drugmetabolizing enzymes in adults: A review of in vivo cytochrome P450 phenotyping probes. Pharmacogenetics. 2000;10:187–216.

30. Bjornsson, T.D., Callaghan, J.T., Einolf, H.J. et al. The conduct of in vitro and in vivo drug-drug interaction studies: A Pharmaceutical Research and Manufacturers of America perspective. Drug Metab. Dispos. 2003;31:815–832.

31. Wilkinson, G.R. Clearance approaches in pharmacology. Pharmacol. Rev. 1987;39:1–47

32. Breimer, D.D. and Schellens, J.H. A ?cocktail? strategy to assess in vivo oxidative drug metabolism in humans. Trends Pharmacol. Sci. 1990;11:223– 225.

33. Christensen, M., Andersson, K., Dalen, P. et al. The Karolinska cocktail for phenotyping of five human cytochrome P450 enzymes. Clin. Pharmacol. Ther. 2003;73:517–528.

34. Ibeanu GC, Blaisdell J, Ghanayem BI, Beyeler C, Benhamou S, Bouchardy C, Wilkinson GR, Dayer P, Daly AK, Goldstein JA. An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in Caucasians. Pharmacogenetics. 1998;8:129–135.

35. Goldstein JA, Ishizaki T, Chiba K, de Morais SM, Bell D, Krahn PM, Evans DA. Frequencies of the defective CYP2C19 alleles responsible for the mephenytoin poor metabolizer phenotype in various Oriental, Caucasian, Saudi Arabian and American black populations. Pharmacogenetics. 1997;7:59–64.

36. Herrlin K, Massele AY, Rimoy G, Alm C, Rais M, Ericsson O, Bertilsson L, Gustafsson LL. Slow chloroguanide metabolism in Tanzanians compared with white subjects and Asian subjects confirms a decreased CYP2C19 activity in relation to genotype. Clin Pharmacol Ther. 2000;68:189–98.

37. Panchabhai TS, Noronha SF, Davis S, Shinde VM, Kshirsagar NA, Gogtay NJ. Evaluation of the activity of CYP2C19 in Gujrati and Marwadi subjects living in Mumbai. BMC Clin Pharmacol. 2006; 6:8.

 

Announcements

Dr. Pramod Kumar Manjhi joined Editor-in-Chief since July 2021 onwards

COPE guidelines for Reviewers

SCOPUS indexing: 2014, 2019 to 2021


Awards, Research and Publication incentive Schemes by IJCRR

Best Article Award: 

One article from every issue is selected for the ‘Best Article Award’. Authors of selected ‘Best Article’ are rewarded with a certificate. IJCRR Editorial Board members select one ‘Best Article’ from the published issue based on originality, novelty, social usefulness of the work. The corresponding author of selected ‘Best Article Award’ is communicated and information of award is displayed on IJCRR’s website. Drop a mail to editor@ijcrr.com for more details.

Women Researcher Award:

This award is instituted to encourage women researchers to publish her work in IJCRR. Women researcher, who intends to publish her research work in IJCRR as the first author is eligible to apply for this award. Editorial Board members decide on the selection of women researchers based on the originality, novelty, and social contribution of the research work. The corresponding author of the selected manuscript is communicated and information is displayed on IJCRR’s website. Under this award selected women, the author is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.

Emerging Researcher Award:

‘Emerging Researcher Award’ is instituted to encourage student researchers to publish their work in IJCRR. Student researchers, who intend to publish their research or review work in IJCRR as the first author are eligible to apply for this award. Editorial Board members decide on the selection of student researchers for the said award based on originality, novelty, and social applicability of the research work. Under this award selected student researcher is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.


Best Article Award

A study by Dorothy Ebere Adimora et al. entitled \"Remediation for Effects of Domestic Violence on Psychological well-being, Depression and Suicide among Women During COVID-19 Pandemic: A Cross-cultural Study of Nigeria and Spain\" is awarded Best Article of Vol 14 issue 23
A study by Muhas C. et al. entitled \"Study on Knowledge & Awareness About Pharmacovigilance Among Pharmacists in South India\" is awarded Best article for Vol 14 issue 22
A study by Saurabh Suvidha entitled \"A Case of Mucoid Degeneration of Uterine Fibroid with Hydrosalphinx and Ovarian Cyst\" is awarded Best article of Vol 14 issue 21
A study by Alice Alice entitled \"Strengthening of Human Milk Banking across South Asian Countries: A Next Step Forward\" is awarded Best article of Vol 14 issue 20
A study by Sathyanarayanan AR et al. entitled \"The on-task Attention of Individuals with Autism Spectrum Disorder-An Eye Tracker Study Using Auticare\" is awarded Best article of Vol 14 issue 19
A study by Gupta P. et al. entitled \"A Short Review on \"A Novel Approach in Fast Dissolving Film & their Evaluation Studies\" is awarded Best Article of Vol 14 issue 18.
A study by Shafaque M. et al. entitled \"A Case-Control Study Performed in Karachi on Inflammatory Markers by Ciprofloxacin and CoAmoxicillin in Patients with Chronic Suppurative Otitis Media\" is awarded Best Article of Vol 14 issue 17
A study by Ali Nawaz et al. entitled \"A Comparative Study of Tubeless versus Standard Percutaneous Nephrolithotomy (PCNL) \? A Randomized Controlled Study\" is awarded Best Article for Vol 14 issue 16.
A study by Singh R. et al. entitled \"A Prospective Study to Find the Association of Astigmatism in Patients of Vernal Keratoconjunctivitis (VKC) in a Tertiary Health Care Centre in India (Vindhya Region MP)\" is awarded Best Article for Vol 14 issue 15
A Study by Humaira Tahir et al. entitled "Comparison of First Analgesic Demand after Major Surgeries of Obstetrics and Gynecology between Pre-Emptive Versus Intra-Operative Groups by Using Intravenous Paracetamol: A Cross-Sectional Study" is awarded Best Article for Vol 14 issue 14
A Study by Monica K. entitled "Risk Predictors for Lymphoma Development in Sjogren Syndrome - A Systematic Review" is awarded Best Article for Vol 14 issue 13
A Study by Mokhtar M Sh et al. entitled "Prevalence of Hospital Mortality of Critically Ill Elderly Patients" is awarded Best Article for Vol 14 issue 12
A Study by Vidya S. Bhat et al. entitled "Effect of an Indigenous Cleanser on the Microbial Biofilm on Acrylic Denture Base - A Pilot Study" is awarded Best Article for Vol 14 issue 11
A Study by Pandya S. et al. entitled "Acute and 28-Day Repeated Dose Subacute Toxicological Evaluation of Coroprotect Tablet in Rodents" is awarded Best Article for Vol 14 issue 10
A Study by Muhammad Zaki et al. entitled "Effect of Hemoglobin Level on the Severity of Acute Bronchiolitis in Children: A Case-Control Study" is awarded Best Article for Vol 14 issue 09
A Study by Vinita S & Ayushi S entitled "Role of Colour Doppler and Transvaginal Sonography for diagnosis of endometrial pathology in women presenting with Abnormal Uterine Bleeding" is awarded Best Article for Vol 14 issue 08
A Study by Prabhu A et al. entitled "Awareness of Common Eye Conditions among the ASHA (Accredited Social Health Activist) Workers in the Rural Communities of Udupi District- A Pilot Study" is awarded Best Article for Vol 14 issue 07
A Study by Divya MP et al. entitled "Non-Echoplanar Diffusion-Weighted Imaging and 3D Fiesta Magnetic Resonance Imaging Sequences with High Resolution Computed Tomography Temporal Bone in Assessment and Predicting the Outcome of Chronic Suppurative Otitis Media with Cholesteatoma" is awarded Best Article for Vol 14 issue 06
A Study by Zahoor Illahi Soomro et al. entitled "Functional Outcomes of Fracture Distal Radius after Fixation with Two Different Plates: A Retrospective Comparative Study" is awarded Best Article for Vol 14 issue 05
A Study by Ajai KG & Athira KN entitled "Patients’ Gratification Towards Service Delivery Among Government Hospitals with Particular Orientation Towards Primary Health Centres" is awarded Best Article for Vol 14 issue 04
A Study by Mbungu Mulaila AP et al. entitled "Ovarian Pregnancy in Kindu City, D.R. Congo - A Case Report" is awarded Best Article for Vol 14 issue 03
A Study by Maryam MJ et al. entitled "Evaluation Serum Chemerin and Visfatin Levels with Rheumatoid Arthritis: Possible Diagnostic Biomarkers" is awarded Best Article for Vol 14 issue 02
A Study by Shanthan KR et al. entitled "Comparison of Ultrasound Guided Versus Nerve Stimulator Guided Technique of Supraclavicular Brachial Plexus Block in Patients Undergoing Upper Limb Surgeries" is awarded Best Article for Vol 14 issue 01
A Study by Amol Sanap et al. entitled "The Outcome of Coxofemoral Bypass Using Cemented Bipolar Hemiarthroplasty in the Treatment of Unstable Intertrochanteric Fracture of Femur in a Rural Setup" is awarded Best Article Award of Vol 13 issue 24
A Study by Manoj KP et al. entitled "A Randomized Comparative Clinical Trial to Know the Efficacy of Ultrasound-Guided Transversus Abdominis Plane Block Against Multimodal Analgesia for Postoperative Analgesia Following Caesarean Section" is awarded Best Article Award of Vol 13 issue 23
A Study by Karimova II et al. entitled "Changes in the Activity of Intestinal Carbohydrases in Alloxan-Induced Diabetic Rats and Their Correction with Prenalon" is awarded Best Article of Vol 13 issue 22
A Study by Ashish B Roge et al. entitled "Development, Validation of RP-HPLC Method and GC MS Analysis of Desloratadine HCL and It’s Degradation Products" is awarded Best Article of Vol 13 issue 21
A Study by Isha Gaurav et al. entitled "Association of ABO Blood Group with Oral Cancer and Precancer – A Case-control Study" is awarded Best Article for Vol 13 issue 20
A Study by Amr Y. Zakaria et al. entitled "Single Nucleotide Polymorphisms of ATP-Binding Cassette Gene(ABCC3 rs4793665) affect High Dose Methotrexate-Induced Nephrotoxicity in Children with Osteosarcoma" is awarded Best Article for Vol 13 issue 19
A Study by Kholis Ernawati et al. entitled "The Utilization of Mobile-Based Information Technology in the Management of Dengue Fever in the Community Year 2019-2020: Systematic Review" is awarded Best Article for Vol 13 issue 18
A Study by Bhat Asifa et al. entitled "Efficacy of Modified Carbapenem Inactivation Method for Carbapenemase Detection and Comparative Evaluation with Polymerase Chain Reaction for the Identification of Carbapenemase Producing Klebsiella pneumonia Isolates" is awarded Best Article for Vol 13 issue 17
A Study by Gupta R. et al. entitled "A Clinical Study of Paediatric Tracheostomy: Our Experience in a Tertiary Care Hospital in North India" is awarded Best Article for Vol 13 issue 16
A Study by Chandran Anand et al. entitled "A Prospective Study on Assessment of Quality of Life of Patients Receiving Sorafenib for Hepatocellular Carcinoma" is awarded Best article for Vol 13 issue 15
A Study by Rosa PS et al. entitled "Emotional State Due to the Covid – 19 Pandemic in People Residing in a Vulnerable Area in North Lima" is awarded Best Article for Vol 13 issue 14
A Study by Suvarna Sunder J et al. entitled "Endodontic Revascularization of Necrotic Permanent Anterior Tooth with Platelet Rich Fibrin, Platelet Rich Plasma, and Blood Clot - A Comparative Study" is awarded Best Article for Vol 13 issue 13
A Study by Mona Isam Eldin Osman et al. entitled "Psychological Impact and Risk Factors of Sexual Abuse on Sudanese Children in Khartoum State" is awarded Best Article for Vol 13 issue 12
A Study by Khaw Ming Sheng & Sathiapriya Ramiah entitled "Web Based Suicide Prevention Application for Patients Suffering from Depression" is awarded Best Article for Vol 13 issue 11
A Study by Purushottam S. G. et al. entitled "Development of Fenofibrate Solid Dispersions for the Plausible Aqueous Solubility Augmentation of this BCS Class-II Drug" is awarded Best article for Vol 13 issue 10
A Study by Kumar S. et al. entitled "A Study on Clinical Spectrum, Laboratory Profile, Complications and Outcome of Pediatric Scrub Typhus Patients Admitted to an Intensive Care Unit from a Tertiary Care Hospital from Eastern India" is awarded Best Article for Vol 13 issue 09
A Study by Mardhiah Kamaruddin et al. entitled "The Pattern of Creatinine Clearance in Gestational and Chronic Hypertension Women from the Third Trimester to 12 Weeks Postpartum" is awarded Best Article for Vol 13 issue 08
A Study by Sarmila G. B. et al. entitled "Study to Compare the Efficacy of Orally Administered Melatonin and Clonidine for Attenuation of Hemodynamic Response During Laryngoscopy and Endotracheal Intubation in Gastrointestinal Surgeries" is awarded Best Article for Vol 13 issue 07
A Study by M. Muthu Uma Maheswari et al. entitled "A Study on C-reactive Protein and Liver Function Tests in Laboratory RT-PCR Positive Covid-19 Patients in a Tertiary Care Centre – A Retrospective Study" is awarded Best Article of Vol 13 issue 06 Special issue Modern approaches for diagnosis of COVID-19 and current status of awareness
A Study by Gainneos PD et al. entitled "A Comparative Evaluation of the Levels of Salivary IgA in HIV Affected Children and the Children of the General Population within the Age Group of 9 – 12 Years – A Cross-Sectional Study" is awarded Best Article of Vol 13 issue 05 Special issue on Recent Advances in Dentistry for better Oral Health
A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" is awarded Best Article of Vol 13 issue 06
A Study by Chen YY and Ghazali SRB entitled "Lifetime Trauma, posttraumatic stress disorder Symptoms and Early Adolescence Risk Factors for Poor Physical Health Outcome Among Malaysian Adolescents" is awarded Best Article of Vol 13 issue 04 Special issue on Current Updates in Plant Biology to Medicine to Healthcare Awareness in Malaysia
A Study by Kumari PM et al. entitled "Study to Evaluate the Adverse Drug Reactions in a Tertiary Care Teaching Hospital in Tamilnadu - A Cross-Sectional Study" is awarded Best Article for Vol 13 issue 05
A Study by Anu et al. entitled "Effectiveness of Cytological Scoring Systems for Evaluation of Breast Lesion Cytology with its Histopathological Correlation" is awarded Best Article of Vol 13 issue 04
A Study by Sharipov R. Kh. et al. entitled "Interaction of Correction of Lipid Peroxidation Disorders with Oxibral" is awarded Best Article of Vol 13 issue 03
A Study by Tarek Elwakil et al. entitled "Led Light Photobiomodulation Effect on Wound Healing Combined with Phenytoin in Mice Model" is awarded Best Article of Vol 13 issue 02
A Study by Mohita Ray et al. entitled "Accuracy of Intra-Operative Frozen Section Consultation of Gastrointestinal Biopsy Samples in Correlation with the Final Histopathological Diagnosis" is awarded Best Article for Vol 13 issue 01
A Study by Badritdinova MN et al. entitled "Peculiarities of a Pain in Patients with Ischemic Heart Disease in the Presence of Individual Combines of the Metabolic Syndrome" is awarded Best Article for Vol 12 issue 24
A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23
A Study by Habiba Suhail et al. entitled "Effect of Majoon Murmakki in Dysmenorrhoea (Usre Tams): A Standard Controlled Clinical Study" is awarded Best Article for Vol 12 issue 22
A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21
A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award


A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award


RSS feed

Indexed and Abstracted in


Antiplagiarism Policy: IJCRR strongly condemn and discourage practice of plagiarism. All received manuscripts have to pass through "Plagiarism Detection Software" test before Toto Macau forwarding for peer review. We consider "Plagiarism is a crime"

IJCRR Code of Conduct: To achieve a high standard of publication, we adopt Good Publishing Practices (updated in 2022) which are inspired by guidelines provided by Committee on Publication Ethics (COPE), Open Access Scholarly Publishers Association (OASPA) and International Committee of Medical Journal Editors (ICMJE)

Disclaimer: International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal.



ABOUT US

International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal

Contact

148, IMSR Building, Ayurvedic Layout,
        Near NIT Complex, Sakkardara,
        Nagpur-24, Maharashtra State, India

editor@ijcrr.com

editor.ijcrr@gmail.com


Copyright © 2024 IJCRR. Specialized online journals by ubijournal .Website by Ubitech solutions