Effect of Rifampicin on BMS-663068 in Healthy Volunteers

May/June 2013

A study presented at the 14th International Workshop on Clinical Pharmacology showed the effects of P-glycoprotein (P-gp) and Cytochrome P450 3A4 (CYP3A4) on BMS-626529 AUC and Cmax, with clinically significant reductions.

BMS-663068 is a pro-drug of BMS-626529. BMS-626529 is a substrate of the P-gp transporter and primarily metabolized by an esterase-mediated hydrolysis pathway and, to a minor extent, CYP3A4. The study evaluated the effects of rifampicin on the pharmacokinetics (PK) of BMS-626529 after a single dose of BMS-663068 in healthy male volunteers.

This was an open-label, one sequence, one-way interaction study conducted in 15 participants. Day 1: all participants received a single dose of BMS-663068 1200 mg in the morning with a standard meal (Treatment A). Days 6-12: participants were given rifampicin 600 mg once daily in the evening. Day 11: all participants received a single dose of BMS-663068 1200 mg in the morning with a standard meal (Treatment B).

Samples for BMS-626529 were taken pre-dose and up to 48 hours post-dose on days 1 and 11. All participants were monitored for adverse events.

Following administration of BMS-663068, the investigators found the ratios of geometric means for BMS-626529 AUCinf and Cmax with and without rifampicin were,0.181 (90% CI 0.163-0.200) and 0.241 (90% CI 0.208-0.279), respectively. Median Tmax, mean T1/2 and mean CTL/F values were: 5 and 4 hours, 6.29 and 6.84 hours and 686 mL/hr and 3841 L/hr, respectively.

The investigators noted that the similar size of reduction in both AUC and Cmax in conjunction with a similar elimination rate suggested that the interaction is likely to be primarily mediated by P-gp induction but a contribution of CYP3A4 could not be ruled out.

They concluded that this study demonstrates the effects of the P-gp and CYP3A4 inducer rifampicin on BMS AUC and Cmax, with a clinically significant reduction by 82 and 76% respectively.


Hruska M et al. The effect of rifampin on the phamacokinetics of the HIV-1 attachment inhibitor pro-drug BMS-663068 in healthy subjects. 14th International Workshop on Clinical Pharmacology. 22-24 April 2013. Amsterdam. Poster abstract P_05.

This article was provided by HIV i-Base. It is a part of the publication HIV Treatment Bulletin. Visit HIV i-Base's website to find out more about their activities, publications and services.

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