{"id":33854,"date":"2018-04-16T08:33:51","date_gmt":"2018-04-16T08:33:51","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=33854"},"modified":"2018-04-16T09:25:20","modified_gmt":"2018-04-16T09:25:20","slug":"twice-daily-bictegravir-does-not-overcome-reduced-concentrations-with-rifampicin","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/33854","title":{"rendered":"Twice-daily bictegravir does not overcome drug interaction with rifampicin"},"content":{"rendered":"

\"\"Polly Clayden, HIV i-Base<\/strong><\/p>\n

Twice daily dosing of bictegravir is not sufficient to mitigate the induction effect of rifampicin and still achieve adequate bictegravir concentrations. <\/strong><\/p>\n

Results from a drug-drug interaction study of bictegravir (BIC) and rifampicin (RIF) conducted in HIV negative participants were included in an oral presentation at CROI 2018.<\/p>\n

BIC is primarily eliminated by the drug metabolising enzymes CYP3A and UGT1A1. RIF is well-known to be a potent inducer of metabolising enzymes.<\/p>\n

A previous study looking at once daily coadministration of the two drugs showed a reduction in BIC concentrations of approximately 75%. This study evaluated the pharmacokinetics (PK) of BIC given twice daily with RIF.<\/p>\n

The was a phase 1, open label study with a parallel design. Participants were enrolled into one of two cohorts \u2013 26 per cohort.<\/p>\n

Cohort 1 participants received the fixed dose combination BIC\/emtricitabine\/tenofovir alafenamide (B\/F\/TAF) 50\/200\/25 mg once daily for 28 days. Cohort 2 participants received B\/F\/TAF twice daily plus RIF 600 mg once daily, for 28 days.<\/p>\n

Intensive sampling was performed on day 28. Statistical comparisons for BIC used geometric least squares mean (GLSM) ratios and associated 90% confidence intervals with B\/F\/TAF once daily as reference.<\/p>\n

This evaluation found BIC AUC0-24h and Cmax were decreased approximately 61% and 47%, respectively, versus B\/F\/TAF once daily alone.<\/p>\n

BIC Ctrough GLSM was approximately 80% lower, as compared with that with B\/F\/TAF once daily.<\/p>\n

These findings showed that twice daily administration of B\/F\/TAF with RIF does not mitigate the induction effect sufficiently to give BIC Ctrough concentrations associated with the B\/F\/TAF registrational phase 3 studies.<\/p>\n

comment<\/h3>\n

Simple HIV and TB co-treatment is essential for low- and middle-income countries so if BIC cannot be administered with RIF this is one reason to suggest this is not good candidate for optimised ART.\u00a0<\/strong><\/p>\n

Reference<\/p>\n

Custodio JM et al. Pharmacokinetics of bictegravir administered twice daily in combination with rifampin. 25th CROI. Boston. 4\u20137 March 2018.\u2028 Oral abstract 34.
\nwww.croiconference.org\/sessions\/pharmacokinetics-bictegravir-administered-twice-daily-combination-rifampin<\/a> (abstract)
\nwww.croiwebcasts.org\/console\/player\/37074<\/a> (webcast)<\/p>\n","protected":false},"excerpt":{"rendered":"

Polly Clayden, HIV i-Base Twice daily dosing of bictegravir is not sufficient to mitigate the induction effect of rifampicin and still achieve adequate bictegravir concentrations. Results from a drug-drug interaction study of bictegravir (BIC) and rifampicin (RIF) conducted in HIV …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,34,37],"tags":[],"class_list":["post-33854","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-pk-and-drug-interactions","category-tb-coinfection"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/33854","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\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=33854"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/33854\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=33854"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=33854"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=33854"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}