{"id":21388,"date":"2013-05-29T16:01:07","date_gmt":"2013-05-29T16:01:07","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=21388"},"modified":"2014-05-29T01:08:17","modified_gmt":"2014-05-29T01:08:17","slug":"effect-of-rifampicin-on-bms-663068-in-healthy-volunteers","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/21388","title":{"rendered":"Effect of rifampicin on BMS-663068 in HIV negative volunteers"},"content":{"rendered":"<p><strong>Polly Clayden, HIV i-Base<\/strong><\/p>\n<p><strong>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.<\/strong><\/p>\n<p>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 HIV negative male volunteers.<\/p>\n<p>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 &#8211; 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).<\/p>\n<p>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.<\/p>\n<p>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 \u2013 0.200) and 0.241 (90% CI 0.208 \u2013 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.<\/p>\n<p>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.<\/p>\n<p>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.<\/p>\n<p>Reference:<\/p>\n<p>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.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Polly Clayden, HIV i-Base 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 &hellip;<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,34],"tags":[174],"class_list":["post-21388","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-pk-and-drug-interactions","tag-pk-workshop-14th-2013"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/21388","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=21388"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/21388\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=21388"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=21388"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=21388"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}