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
Bibliographic record
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). 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 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. 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".