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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.
- Source :
-
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques [J Pharm Pharm Sci] 2013; Vol. 16 (4), pp. 502-10. - Publication Year :
- 2013
-
Abstract
- Purpose: To determine the effects of CYP3A5 polymorphisms on carbamazepine (CBZ) pharmacokinetic parameters when CBZ is used either as monotherapy or co-administered with phenytoin (PHT), phenobarbital (PB) or valproic acid (VPA).<br />Methods: Retrospective data were collected from an electronic database and medical records. Blood samples were obtained and drug concentrations analyzed as a part of routine therapeutic drug monitoring (TDM). Screening for wild-type CYP3A5*1 and CYP3A5*3 single nucleotide polymorphism (rs776746) by allelic discrimination assay using real-time polymerase chain reaction technique (real-time PCR) was performed. Pharmacokinetic parameters of CBZ; clearance and dose-adjusted CBZ levels in patients with different genotypes were calculated and compared.<br />Results: Of the 70 patients assessed, 8 (11%) patients were homozygous CYP3A5*1/*1, 28 (40%) patients were heterozygous CYP3A5*1/*3, and 34 (49%) patients were homozygous CYP3A5*3/*3. The CBZ clearance and dose-adjusted CBZ levels did not significantly differ between patients with CYP3A5*1 and CYP3A5*3 alleles when CBZ was used as monotherapy. For patients who used CBZ in combination with an enzyme-inducing antiepileptic drug (AED: PHT or PB), individuals carrying the CYP3A5*1 allele (CYP3A5 expressers) showed a trend of having higher CBZ clearance and lower dose-adjusted CBZ level as compared to individuals carrying the CYP3A5*3 allele, even though no statistical significance was recorded. Nevertheless, it was observed that AEDs significantly increased CBZ clearance only in patients carrying the active CYP3A5*1 allele.<br />Conclusions: When CBZ was used in combination with enzyme-inducing AED, CYP3A5 expressers yielded a trend toward greater susceptibility to change in CBZ clearance and showed lower dose-adjusted CBZ levels compared to CYP3A5 non-expressers. The dosage regimen should be adjusted accordingly to gain a better clinical outcome.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Anticonvulsants administration & dosage
Asian People
Carbamazepine administration & dosage
Drug Interactions
Female
Genotype
Humans
Male
Middle Aged
Young Adult
Anticonvulsants pharmacokinetics
Carbamazepine pharmacokinetics
Cytochrome P-450 CYP3A genetics
Phenobarbital administration & dosage
Phenytoin administration & dosage
Valproic Acid administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1482-1826
- Volume :
- 16
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
- Publication Type :
- Academic Journal
- Accession number :
- 24210059
- Full Text :
- https://doi.org/10.18433/j3q888