ABSTRACT
PURPOSE: This study was the first to evaluate the effect of CYP3A5*3 gene polymorphisms on plasma concentration of perampanel (PER) in Chinese pediatric patients with epilepsy. METHODS: We enrolled 98 patients for this investigation. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final checkup. RESULTS: The plasma concentration showed a linear correlation with the daily dose taken ( r â =â 0.17; P â <â 0.05). The ineffective group showed a significantly lower plasma concentration of PER (490.5â ±â 297.1 vs. 633.8â ±â 305.5â µg/ml; P â =â 0.019). For the mean concentration-to-dose (C/D) ratio, the ineffective group showed a significantly lower C/D ratio of PER (3.2â ±â 1.7 vs. 3.8â ±â 2.0; P â =â 0.040). The CYP3A5*3 CC genotype exhibited the highest average plasma concentration of PER at 562.8â ±â 293.9 ng/ml, in contrast to the CT and TT genotypes at 421.1â ±â 165.6 ng/ml and 260.0â ±â 36.1 ng/ml. The mean plasma PER concentration was significantly higher in the adverse events group (540.8â ±â 285.6 vs. 433.0â ±â 227.2 ng/ml; P â =â 0.042). CONCLUSION: The CYP3A5*3 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A5*3 genetic genotype should be factored in when prescribing PER to patients with epilepsy.
ABSTRACT
OBJECTIVE: To clone heavy-chain and light-chain variable region (VH and VL) gene of mouse-anti-human CD71 monoclonal antibody (mAb). METHOD: One-step method was used to extract total RNA, and a set of oligonucleotide primers were designed to amplify the cDNAs with reverse transcriptase-polymerase chain reaction (RT-PCR), and the resultant products were respectively cloned into PMD18-T vector and their sequences analyzed. RESULTS: The PCR product obtained with the oligonucleotide primers for the variable region of mouse immunoglobulin heavy chain was about 350 bp and that with oligonucleotide primers for the light chain was about 320 bp, and their DNA sequences were determined. CONCLUSION: The length of the cloned heavy chain variable region was 348 bp, belonging to mouse heavy-chain subgroup II(A); the light-chain variable region was 336 bp that belongs to mouse kappa light-chain subgroup II.
