摘要
Objective To systematically assess the effect of CYP450 inhibitors on the pharmacokinetics and safety of VORI.Methods:Cochrane Library,PubMed,Embase,CNKI,CBM and WanFang databases were searched up to January 26 th 2016.Meta analyses were performed with RevMan5.3,and risk ratios(RRs) and mean differences(MDs) with 95%confidence intervals(CIs) were calculated.Results:Seventeen studies were included:1 parallel RCT,5 cross-over RCTs,4 single-arm before-and-after studies,6 cohort studies and 1 case report.Compared with no-combined group,the group of VORI plus omeprazole had a significantly higher occurrence of hepatic dysfunction(RR = 4.11,95%CI 1.12-15.08,P = 0.03);however,no difference of neurologic dysfunction was found between VORI plus omeprazole and control group(RR = 5.20,95%CI0.52-52.47,P = 0.16).Similarly for the C_(min) of VORI,there was no difference between combined and no-combined omeprazole groups(MD = 0.18,95%CI 0.00-0.36,P=0.05).Pantoprazole,rabeprazole,cimetidine,erythromycin and contraceptive significantly increased the peak concentration and concentration-time curve(AUC) of VORI;however,indinavir and etravirine had no significant effect.The variation of pharmacokinetic parameters of VORI co-administeredwith esomeprazole,azithromycin and ritonavir indicated conflict effects.Conclusions:Co-administration of VORI and CYP450 inhibitors was safe except omeprazole.Although the C_(max) and AUC of VORI were increased while co-administrated with CYP450 inhibitors,no significantly effect on clinical practice was observed.
Objective To systematically assess the effect of CYP450 inhibitors on the pharmacokinetics and safety of VORI.Methods:Cochrane Library,PubMed,Embase,CNKI,CBM and WanFang databases were searched up to January 26 th 2016.Meta analyses were performed with RevMan5.3,and risk ratios(RRs) and mean differences(MDs) with 95%confidence intervals(CIs) were calculated.Results:Seventeen studies were included:1 parallel RCT,5 cross-over RCTs,4 single-arm before-and-after studies,6 cohort studies and 1 case report.Compared with no-combined group,the group of VORI plus omeprazole had a significantly higher occurrence of hepatic dysfunction(RR = 4.11,95%CI 1.12-15.08,P = 0.03);however,no difference of neurologic dysfunction was found between VORI plus omeprazole and control group(RR = 5.20,95%CI0.52-52.47,P = 0.16).Similarly for the C_(min) of VORI,there was no difference between combined and no-combined omeprazole groups(MD = 0.18,95%CI 0.00-0.36,P=0.05).Pantoprazole,rabeprazole,cimetidine,erythromycin and contraceptive significantly increased the peak concentration and concentration-time curve(AUC) of VORI;however,indinavir and etravirine had no significant effect.The variation of pharmacokinetic parameters of VORI co-administeredwith esomeprazole,azithromycin and ritonavir indicated conflict effects.Conclusions:Co-administration of VORI and CYP450 inhibitors was safe except omeprazole.Although the C_(max) and AUC of VORI were increased while co-administrated with CYP450 inhibitors,no significantly effect on clinical practice was observed.
引文
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