RESUMO
Objective To explore the effect of CYP2C19 gene polymorphism on clopidogrel plasma concentration, rate of platelet inhibition and safety. Methods We screen the patients who took clopidogrel after PCI in our hospital, according to the inclusion and exclusion criteria. Blood samples were collected on the 6th day after clopidogrel administration. Clopidogrel blood concentration was determine by RP-HPLC. The CYP2C19 genotype was detected by non-amplified immune hybridization. The rate of platelet inhibition was evaluated by the thromboelastogram. The results were analyzed by SPSS 20.0 software. Results A total of 87 patients were recruited, including 46 males and 41 females. Among them, 34 cases were fast metabolism. 38 cases were medium metabolism. 15 cases were slow metabolism. The result showed that there was no significant difference in drug concentration between fast and intermediate metabolism(P=0.667). There was a significant difference in drug concentration between slow metabolism and fast metabolism or medium metabolism(P<0.05). Analysis of variance and chi-square test showed that CYP2C19 gene polymorphism has a significant effect on clopidogrel platelet inhibition rate and safety (P<0.05). Conclusion Guiding clopidogrel clinical medication based on CYP2C19 genotype alone does not necessarily achieve better therapeutic effects. CYP2C19 genotype detection and blood concentration monitoring can be combined to guide the clinical individualized administration of clopidogrel
RESUMO
Objective: To examine the correlation between paliperidone plasma concentration and clinical efficacy in the patients with schizophrenia. Methods:Totally 50 schizophrenia patients were treated by paliperidone. The plasma concentration of paliperidone was monitored by RP-HPLC at the weekend of the 2 nd, 4 th and 6 th week, the clinical efficacy was evaluated using the positive and negative syndrome scale ( PANSS) , and the correlation between paliperidone plasma concentration and clinical efficacy was analyzed. Results:The mean plasma concentration of paliperidone was (31. 89 ± 17. 36) ng·ml-1 at the weekend of the 6th week, and no cor-relation was found between paliperidone plasma concentration and the clinical efficacy (r=0. 146,P=0. 074). Paliperidone plasma concentration in 12 patients with adverse drug reactions (ADR) was higher than that in the patients without ADR [(45. 87 ± 19. 21)ng ·ml-1 vs (27. 06 ± 11. 13) ng·ml-1, P <0. 01]. Conclusion: Paliperidone plasma concentration shows significant individual differences. With the increase of paliperidone plasma concentration, clinical efficacy isn't necessarily improved, while the incidence of ADR may be increased. Therefore, the monitoring of paliperidone plasma concentration is recommended to optimize the therapeutic reg-imen.
RESUMO
Aim To establish an UPLC-ESI-MS method for determination of asiaticoside and investigate its application to pharmacokinetic study in rats.Methods Eight rats were given 40 mg·kg~(-1) asiaticoside iv respectively.Drug plasma concentration was determined by UPLC-ESI-MS.Pharmacokinetic parameters were evaluated.Results Calibration curves were linear over 0.038～7.6 mg·L~(-1) and LLOQ was 38 μg·L~(-1),the recoveries of asiaticoside from plasma were larger than 95%,and RSD of inter-day and intra-day assay were below 10%.After iv administration of 40 mg·kg~(-1) asiaticoside,the pharmacokinetic parameters of AUC(0-t),T(1)/(2)β,CL,Vd were (81 443.67±57 156.81) μg·L~(-1)·min~(-1),(23.44±9.60) min,(0.19±0.07) L·min~(-1)·kg~(-1),(8.92±6.68) L·kg~(-1),respectively.Conclusion The method described in this report was sensitive and specific,and suitable for pharmacokinetic studies of asiaticoside in rats.