Effect of intermittent rifampicin on the pharmacokinetics and safety of raltegravir

Previous studies of raltegravir and rifampicin have not studied the interaction when rifampicin is dosed intermittently. This study aimed to assess the pharmacokinetics of twice daily raltegravir and intermittently dosed rifampicin. This was a prospective, open, single-arm, three-part, controlled study in healthy volunteers. Over a period of 38 days subjects received 5 days of standard-dose raltegravir (400 mg twice daily) followed by 28 days of standard-dose raltegravir plus rifampicin three times a week followed by 5 days of high-dose (800 mg twice daily) raltegravir plus rifampicin three times a week. Pharmacokinetic sampling was performed on days 5, 33 and 38. Raltegravir pharmacokinetic parameters were determined by non-compartmental analysis and reported as geometric means and 90% CIs. ClinicalTrials.gov: NCT01424826. Sixteen subjects (12 females) completed the study. Raltegravir trough plasma concentration (C12) was significantly lower in the presence of rifampicin when dosed at 400 mg twice daily (40%), which was not observed with 800 mg twice daily dosing. Raltegravir Cmax and AUC0-12 were both significantly higher in the presence of rifampicin when dosed at 800 mg twice daily (76% and 84%, respectively), but this dose was well tolerated. This study suggests that rifampicin induction of raltegravir is comparable between daily and intermittent rifampicin. In the absence of definitive clinical efficacy data to suggest otherwise, doses of 800 mg of raltegravir twice daily with rifampicin thrice weekly are well tolerated and yield higher AUCs and comparable C12 when compared with raltegravir alone.