Influence of cytochrome P450 3A5 (CYP3A5) genetic polymorphism on dose-adjusted plasma levels of carbamazepine in epileptic patients in South Indian population
AIM: The aim of the study was to compare the dose-adjusted plasma levels of carbamazepine (CBZ) among expressers and nonexpressers of cytochrome P450 3A5 (CYP3A5)* 3 genotypes. SUBJECTS AND METHODS: The study was carried out in 100 epileptic patients who were on CBZ monotherapy. Steady-state plasma...
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| Published in | Indian journal of pharmacology Vol. 51; no. 6; pp. 384 - 388 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
India
Wolters Kluwer India Pvt. Ltd
01.11.2019
Medknow Publications and Media Pvt. Ltd Medknow Publications & Media Pvt. Ltd Wolters Kluwer - Medknow |
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| Online Access | Get full text |
| ISSN | 0253-7613 1998-3751 1998-3751 |
| DOI | 10.4103/ijp.IJP_122_19 |
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| Abstract | AIM: The aim of the study was to compare the dose-adjusted plasma levels of carbamazepine (CBZ) among expressers and nonexpressers of cytochrome P450 3A5 (CYP3A5)* 3 genotypes.
SUBJECTS AND METHODS: The study was carried out in 100 epileptic patients who were on CBZ monotherapy. Steady-state plasma CBZ levels were measured using reverse-phase high-performance liquid chromatography method, and genotyping of CYP3A5 was done using real-time polymerase chain reaction method.
RESULTS: Patients inheriting CYP3A5*3/*3 variant (nonexpressers) had an increased plasma concentration of CBZ (4.86 μg/ml) when compared to patients inheriting either CYP3A5*1/*1 or CYP3A5*1/*3 (expressers) (4.3 μg/ml, P = 0.004). Nonexpressers had significantly increased plasma concentrations of CBZ when adjusted for dose and weight when compared to expressers (P < 0.002 and P < 0.001, respectively). The frequency of adverse reactions in expressers and nonexpressers was 12% and 9%, respectively.
CONCLUSION: There is a significant influence of CYP3A5*3 genetic polymorphism (6986A>G) on dose-adjusted plasma levels of CBZ in epileptic patients in the South Indian population. |
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| AbstractList | The aim of the study was to compare the dose-adjusted plasma levels of carbamazepine (CBZ) among expressers and nonexpressers of cytochrome P450 3A5 (CYP3A5)* 3 genotypes.AIMThe aim of the study was to compare the dose-adjusted plasma levels of carbamazepine (CBZ) among expressers and nonexpressers of cytochrome P450 3A5 (CYP3A5)* 3 genotypes.The study was carried out in 100 epileptic patients who were on CBZ monotherapy. Steady-state plasma CBZ levels were measured using reverse-phase high-performance liquid chromatography method, and genotyping of CYP3A5 was done using real-time polymerase chain reaction method.SUBJECTS AND METHODSThe study was carried out in 100 epileptic patients who were on CBZ monotherapy. Steady-state plasma CBZ levels were measured using reverse-phase high-performance liquid chromatography method, and genotyping of CYP3A5 was done using real-time polymerase chain reaction method.Patients inheriting CYP3A5*3/*3 variant (nonexpressers) had an increased plasma concentration of CBZ (4.86 μg/ml) when compared to patients inheriting either CYP3A5*1/*1 or CYP3A5*1/*3 (expressers) (4.3 μg/ml, P = 0.004). Nonexpressers had significantly increased plasma concentrations of CBZ when adjusted for dose and weight when compared to expressers (P < 0.002 and P < 0.001, respectively). The frequency of adverse reactions in expressers and nonexpressers was 12% and 9%, respectively.RESULTSPatients inheriting CYP3A5*3/*3 variant (nonexpressers) had an increased plasma concentration of CBZ (4.86 μg/ml) when compared to patients inheriting either CYP3A5*1/*1 or CYP3A5*1/*3 (expressers) (4.3 μg/ml, P = 0.004). Nonexpressers had significantly increased plasma concentrations of CBZ when adjusted for dose and weight when compared to expressers (P < 0.002 and P < 0.001, respectively). The frequency of adverse reactions in expressers and nonexpressers was 12% and 9%, respectively.There is a significant influence of CYP3A5*3 genetic polymorphism (6986A>G) on dose-adjusted plasma levels of CBZ in epileptic patients in the South Indian population.CONCLUSIONThere is a significant influence of CYP3A5*3 genetic polymorphism (6986A>G) on dose-adjusted plasma levels of CBZ in epileptic patients in the South Indian population. AIM: The aim of the study was to compare the dose-adjusted plasma levels of carbamazepine (CBZ) among expressers and nonexpressers of cytochrome P450 3A5 (CYP3A5)* 3 genotypes. SUBJECTS AND METHODS: The study was carried out in 100 epileptic patients who were on CBZ monotherapy. Steady-state plasma CBZ levels were measured using reverse-phase high-performance liquid chromatography method, and genotyping of CYP3A5 was done using real-time polymerase chain reaction method. RESULTS: Patients inheriting CYP3A5*3/*3 variant (nonexpressers) had an increased plasma concentration of CBZ (4.86 μg/ml) when compared to patients inheriting either CYP3A5*1/*1 or CYP3A5*1/*3 (expressers) (4.3 μg/ml, P = 0.004). Nonexpressers had significantly increased plasma concentrations of CBZ when adjusted for dose and weight when compared to expressers (P < 0.002 and P < 0.001, respectively). The frequency of adverse reactions in expressers and nonexpressers was 12% and 9%, respectively. CONCLUSION: There is a significant influence of CYP3A5*3 genetic polymorphism (6986A>G) on dose-adjusted plasma levels of CBZ in epileptic patients in the South Indian population. The aim of the study was to compare the dose-adjusted plasma levels of carbamazepine (CBZ) among expressers and nonexpressers of cytochrome P450 3A5 genotypes. The study was carried out in 100 epileptic patients who were on CBZ monotherapy. Steady-state plasma CBZ levels were measured using reverse-phase high-performance liquid chromatography method, and genotyping of was done using real-time polymerase chain reaction method. Patients inheriting variant (nonexpressers) had an increased plasma concentration of CBZ (4.86 μg/ml) when compared to patients inheriting either or (expressers) (4.3 μg/ml, = 0.004). Nonexpressers had significantly increased plasma concentrations of CBZ when adjusted for dose and weight when compared to expressers ( < 0.002 and < 0.001, respectively). The frequency of adverse reactions in expressers and nonexpressers was 12% and 9%, respectively. There is a significant influence of genetic polymorphism (6986A>G) on dose-adjusted plasma levels of CBZ in epileptic patients in the South Indian population. AIM: The aim of the study was to compare the dose-adjusted plasma levels of carbamazepine (CBZ) among expressers and nonexpressers of cytochrome P450 3A5 (CYP3A5)* 3 genotypes. SUBJECTS AND METHODS: The study was carried out in 100 epileptic patients who were on CBZ monotherapy. Steady-state plasma CBZ levels were measured using reverse-phase high-performance liquid chromatography method, and genotyping of CYP3A5 was done using real-time polymerase chain reaction method. RESULTS: Patients inheriting CYP3A5*3/*3 variant (nonexpressers) had an increased plasma concentration of CBZ (4.86 μg/ml) when compared to patients inheriting either CYP3A5*1/*1 or CYP3A5*1/*3 (expressers) (4.3 μg/ml, P = 0.004). Nonexpressers had significantly increased plasma concentrations of CBZ when adjusted for dose and weight when compared to expressers (P < 0.002 and P < 0.001, respectively). The frequency of adverse reactions in expressers and nonexpressers was 12% and 9%, respectively. CONCLUSION: There is a significant influence of CYP3A5*3 genetic polymorphism (6986A>G) on dose-adjusted plasma levels of CBZ in epileptic patients in the South Indian population. |
| Audience | Academic |
| Author | Narayan, Sunil Adithan, Surendiran Ramasamy, Kesavan Ganesapandian, Mahalakshmi |
| AuthorAffiliation | Department of Pharmacology, JIPMER, Puducherry, India 1 Department of Neurology, JIPMER, Puducherry, India |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32029960$$D View this record in MEDLINE/PubMed |
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| Copyright | Copyright: © 2020 Indian Journal of Pharmacology. COPYRIGHT 2019 Medknow Publications and Media Pvt. Ltd. 2019. This work is published under https://creativecommons.org/licenses/by-nc-sa/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Copyright: © 2020 Indian Journal of Pharmacology 2020 |
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| Keywords | cytochrome P450 3A5 genetic polymorphisms Carbamazepine pharmacogenetics |
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| References_xml | – start-page: 502 year: 2013 ident: key-10.4103/0253-7613.276041-9 article-title: Effect of CYP3A5 genotypes on the pharmacokinetics of carbamazepine when used as monotherapy or co-administered with phenytoin, phenobarbital or valproic acid in Thai patients publication-title: J Pharm Pharm Sci doi: 10.18433/J3Q888 – start-page: 27 issn: 0971-5916 year: 2014 ident: key-10.4103/0253-7613.276041-2 article-title: Distribution of genetic polymorphisms of genes encoding drug metabolizing enzymes & drug transporters – A review with Indian perspective publication-title: Indian J Med Res – start-page: 105 year: 1984 ident: key-10.4103/0253-7613.276041-4 article-title: Antiepileptic agents – Primidone, phenobarbital, phenytoin, and carbamazepine by reversed-phase liquid chromatography publication-title: Clin Chem doi: 10.1093/clinchem/30.1.105 – start-page: 569 year: 2009 ident: key-10.4103/0253-7613.276041-6 article-title: Effect of CYP3A5 * 3 genotype on serum carbamazepine concentrations at steady-state in Korean epileptic patients publication-title: J Clin Pharm Ther doi: 10.1111/j.1365-2710.2009.01057.x – start-page: 35 year: 2013 ident: key-10.4103/0253-7613.276041-8 article-title: Association of carbamazepine major metabolism and transport pathway gene polymorphisms and pharmacokinetics in patients with epilepsy publication-title: Pharmacogenomics doi: 10.2217/pgs.12.180 – start-page: 52 year: 2015 ident: key-10.4103/0253-7613.276041-10 article-title: Effects of CYP3A4/5 and ABCB1 genetic polymorphisms on carbamazepine metabolism and transport in Chinese patients with epilepsy treated with carbamazepine in monotherapy and bitherapy publication-title: Epilepsy Res doi: 10.1016/j.eplepsyres.2015.09.001 – start-page: 906 year: 2011 ident: key-10.4103/0253-7613.276041-1 article-title: PharmGKB summary: Carbamazepine pathway publication-title: Pharmacogenet Genomics doi: 10.1097/FPC.0b013e328348c6f2 – start-page: 383 year: 2001 ident: key-10.4103/0253-7613.276041-5 article-title: Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression publication-title: Nat Genet doi: 10.1038/86882 – start-page: 489 year: 2009 ident: key-10.4103/0253-7613.276041-3 article-title: Reconstructing Indian population history publication-title: Nature doi: 10.1038/nature08365 – start-page: 93 year: 2015 ident: key-10.4103/0253-7613.276041-7 article-title: CYP3A5 polymorphism in Serbian paediatric epileptic patients on carbamazepine treatment publication-title: Serbian J Exp Clin Res doi: 10.1515/sjecr-2015-0012 |
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| SubjectTerms | African Americans Anticonvulsants Carbamazepine Chromatography Convulsions & seizures Cytochrome Drug dosages Enzymes Epilepsy Genetic aspects Genetic polymorphisms Genetic research Genotypes High performance liquid chromatography Liquid chromatography Metabolism Minority & ethnic groups Polymerase chain reaction Polymorphism Population Primidone Sample size Statistical analysis Studies Time |
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| Title | Influence of cytochrome P450 3A5 (CYP3A5) genetic polymorphism on dose-adjusted plasma levels of carbamazepine in epileptic patients in South Indian population |
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