Effect of CYP3A5*3 on carbamazepine pharmacokinetics in Japanese patients with epilepsy

Shioiri, Takayuki; Nakada, Naoyuki; Ueda, Norihiro; Hagiwara, Takeshi; Hashimoto, Naozumi; Nakagawa, Kazuko; Ishitsu, Takateru

doi:10.1016/j.clpt.2006.02.009

Cited by 34 publications

(38 citation statements)

References 5 publications

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“…This result conflicted with the result from the study by Park et al of 35 Korean epileptic patients, who reported that the CBZ clearance in patients with homozygous CYP3A5*3/*3 was 29% lower than that observed in patients with at least one CYP3A5*1 allele [16]. Seo et al [15] recruited patients who used CBZ as either monotherapy or concurrently with the potent inducer of CYP3A, i.e. PHT and PB, into their study which may confound the effect of CYP3A5 genotypes on CBZ pharmacokinetics.…”

Section: Discussioncontrasting

confidence: 56%

“…Because CYP3A5 may represent up to 50% of the total CYP3A protein in individuals polymorphically expressing CYP3A5, it may have a major role in the variation of CYP3A-mediated drug metabolism [22][23]. A previous study by Seo et al of 144 Japanese epileptic patients reported that patients with CYP3A5*3/*3 exhibited CBZ clearance 8% higher than patients not carrying CYP3A5*3/*3 [15]. This result conflicted with the result from the study by Park et al of 35 Korean epileptic patients, who reported that the CBZ clearance in patients with homozygous CYP3A5*3/*3 was 29% lower than that observed in patients with at least one CYP3A5*1 allele [16].…”

Section: Discussionmentioning

confidence: 99%

“…We excluded pregnant women, patients with hepatic disease or renal disease. Additionally, patients who were concurrently using drugs which may interact with CBZ pharmacokinetics (except PHT, PB and VPA) were excluded, namely verapamil, diltiazem, haloperidol, theophylline, ticlopidine, cimetidine, omeprazole, trazodone, fluoxetine, risperidone, clarithromycin, erythromycin, rifampicin, isoniazid, isotretrinion, gemfibrozil and metronidazole [14][15][16]. Grapefruit consumers, if any, were excluded.…”

Section: Patientsmentioning

confidence: 99%

“…Among several factors that have been reported as influencing the elimination of CBZ, age, body weight, surface area, dose of CBZ, and comedication with PHT, PB, or VPA [8,9,[12][13][14], CYP3A5 polymorphism have more recently received greater focus. Seo et al reported CBZ clearance in patients with CYP3A5*3/*3 to be 8% significantly higher than that in patient with CYP3A5*1/*1 or CYP3A5*1/*3 [15].…”

Section: Introductionmentioning

confidence: 99%

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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

2013

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-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). 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. 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 enzymeinducing 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. 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.

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Section: Discussioncontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

2013

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“…However, due to conflicting reports, the evidence of association between carbamazepine treatment outcomes and CYP3A5 functional variations remains inconclusive. As an example, although CYP3A5 genotype affected serum concentration of carbamazepine in Koreans (15), Chinese (16), and Japanese (17), as well as drug half-life in African-Americans (18), no influence of carbamazepine pharmacokinetics parameters were observed in Caucasian epileptic patients (18). The apparent underlying cause of this discrepancy might be interethnic variability, which represents a multidimensional determinant that comprises both genetic heritage and environment (19,20).…”

Section: Introductionmentioning

confidence: 99%

CYP3A5 Polymorphism In Serbian Paediatric Epileptic Patients On Carbamazepine Treatment

Milovanović

Radosavljevic

Radovanovic

et al. 2015

Serbian Journal of Experimental and Clinical Research

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Pharmacogenetic Variants and Plasma Concentrations of Antiseizure Drugs

Milosavljević,

Manojlović,

Matković

et al. 2024

JAMA Netw Open

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ImportancePrecise estimation of a patient’s drug metabolism capacity is important for antiseizure dose personalization.ObjectiveTo quantify the differences in plasma concentrations for antiseizure drugs associated with variants of genes encoding drug metabolizing enzymes.Data SourcesPubMed, Clinicaltrialsregister.eu, ClinicalTrials.gov, International Clinical Trials Registry Platform, and CENTRAL databases were screened for studies from January 1, 1990, to September 30, 2023, without language restrictions.Study SelectionTwo reviewers performed independent study screening and assessed the following inclusion criteria: appropriate genotyping was performed, genotype-based categorization into subgroups was possible, and each subgroup contained at least 3 participants.Data Extraction and SynthesisThe Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed for data extraction and subsequent quality, validity, and risk-of-bias assessments. The results from the included studies were pooled with random-effect meta-analysis.Main Outcomes and MeasuresPlasma concentrations of antiseizure drugs were quantified with the dose-normalized area under the concentration-time curve, the dose-normalized steady state concentration, or the concentrations after a single dose at standardized dose and sampling time. The ratio of the means was calculated by dividing the mean drug plasma concentrations of carriers and noncarriers of the pharmacogenetic variant.ResultsData from 98 studies involving 12 543 adult participants treated with phenytoin, valproate, lamotrigine, or carbamazepine were analyzed. Studies were mainly conducted within East Asian (69 studies) or White or European (15 studies) cohorts. Significant increases of plasma concentrations compared with the reference subgroup were observed for phenytoin, by 46% (95% CI, 33%-61%) in CYP2C9 intermediate metabolizers, 20% (95% CI, 17%-30%) in CYP2C19 intermediate metabolizers, and 39% (95% CI, 24%-56%) in CYP2C19 poor metabolizers; for valproate, by 12% (95% CI, 4%-20%) in CYP2C9 intermediate metabolizers, 12% (95% CI, 2%-24%) in CYP2C19 intermediate metabolizers, and 20% (95% CI, 2%-41%) in CYP2C19 poor metabolizers; and for carbamazepine, by 12% (95% CI, 3%-22%) in CYP3A5 poor metabolizers.Conclusions and RelevanceThis systematic review and meta-analysis found that CYP2C9 and CYP2C19 genotypes encoding low enzymatic capacity were associated with a clinically relevant increase in phenytoin plasma concentrations, several pharmacogenetic variants were associated with statistically significant but only marginally clinically relevant changes in valproate and carbamazepine plasma concentrations, and numerous pharmacogenetic variants were not associated with statistically significant differences in plasma concentrations of antiseizure drugs.

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Effect of CYP3A5*3 on carbamazepine pharmacokinetics in Japanese patients with epilepsy

Cited by 34 publications

References 5 publications

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

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

CYP3A5 Polymorphism In Serbian Paediatric Epileptic Patients On Carbamazepine Treatment

Pharmacogenetic Variants and Plasma Concentrations of Antiseizure Drugs

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