A meta-analysis of effects of CYP2C9 and CYP2C19 polymorphisms on phenytoin pharmacokinetic parameters

Abstract

Aim: Phenytoin is metabolized through CYP2C9 and CYP2C19 . Polymorphisms of CYP2C9 and CYP2C19 may increase plasma concentration and side effects. Materials & methods: Systematic review and meta-analysis were performed to evaluate the effects of CYP2C9 and CYP2C19 polymorphism on pharmacokinetic parameters. PubMed, Science Direct, Cochrane library, and Thai databases were systematically searched. Results: Eight observational studies, comprising a total of 633 patients were included. Michaelis–Menten constant was significantly higher in the polymorphism of CYP2C9IM/CYP2C19EM and CYP2C9IM/CYP2C19IM groups as compared with the control groups (CYP2C9EM/CYP2C19EM) at 2.16 and 1.55 mg/l (p < 0.00001, p < 0.0001). The maximum rate of action was significantly lower in the control groups as compared with the polymorphism of CYP2C9IM/CYP2C19EM and CYP2C9IM/CYP2C19IM groups at 3.10 and 3.53 mg/kg/day (p = 0.00001, <0.0001). Conclusion: The dosage regimen for patients in the CYP2C9IM group to achieve phenytoin therapeutic levels was 2.1–3.4 mg/kg/day.