{"id":34379,"date":"2018-06-29T08:30:53","date_gmt":"2018-06-29T08:30:53","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=34379"},"modified":"2018-06-29T09:43:12","modified_gmt":"2018-06-29T09:43:12","slug":"no-clinically-relevant-reduction-in-oral-cabotegravir-when-co-administered-with-rifabutin","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/34379","title":{"rendered":"No clinically relevant reduction in oral cabotegravir when co-administered with rifabutin \u00a0"},"content":{"rendered":"<p class=\"HTBsubhead3authorcredit\"><strong><span lang=\"EN-US\">Polly Clayden, HIV i-Base <\/span><\/strong><\/p>\n<p class=\"HTBBODYtext\"><b><span lang=\"EN-US\">Rifabutin (RBT) can be given with oral cabotegravir (CAB) without dose adjustment, according to data presented at the <\/span><\/b><b>19th International Workshop on Clinical Pharmacology. <span lang=\"EN-US\">A modest decrease in plasma CAB following long-acting (LA) administration with RBT is expected.<\/span><\/b><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">CAB is in development as a LA injectable formulation with an oral CAB 30 mg lead-in for treatment and prevention of HIV.<\/span><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Significant interaction between oral CAB and rifampicin (RIF) limits their use together. RBT is chemically similar to RIF but considered a weaker inducer of UGTs and CYP3A. <\/span>CAB is metabolised primarily by UGT1A1, with minor contribution by UGT1A9.<span lang=\"EN-US\">\u00a0\u00a0 <\/span><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">This study evaluated the effect of RBT on the pharmacokinetics (PK) of oral CAB in HIV negative participants. It was phase I, single-centre, open label, two period, fixed-sequence, drug interaction study conducted by the originator manufacturer ViiV Healthcare. <\/span><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Fifteen male participants with a median age of 44 years and weight of 84 kg received oral CAB 30mg once daily for 14 days and then co-administered with RBT 300mg once daily for 14 days. Twelve participants completed as planned. Serial PK sampling was performed on days 14 and 28. <\/span><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Comparing CAB + RBT to CAB alone, the GLS mean ratios were: AUC0\u201324, Cmax, and Ctrough were 0.79 ug*h\/mL (90% CI 0.74 to 0.83), 0.83 ug\/mL (90% CI 0.76 to 0.90) and 0.74 ug\/mL (<\/span>90% CI <span lang=\"EN-US\">0.70 to 0.78), respectively. <\/span><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">RBT increased CAB oral clearance by 27% following repeat dose co-administration and reduced <\/span>AUC0\u201324, Cmax, and Ctrough by 21%, 17% and 26% respectively.<\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Eleven participants reported 24 adverse events \u2013 most were grade 1 and occurred during CAB + RBT co-administration.<\/span><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">The investigators concluded that a 27% increase in clearance does not preclude co-administration of RBT + CAB LA. Simulations will inform strategies for LA regimens and alternative dosing schedules with RBT.<\/span><\/p>\n<p class=\"HTBreference-noindent\"><span lang=\"EN-US\">Reference<\/span><\/p>\n<p class=\"HTBreference-noindent\"><span lang=\"EN-US\">Ford S et al. Rifabutin\u2028 (RBT) decreases cabotegravir (CAB) exposure following oral co-administration. 19th International Workshop on Clinical Pharmacology. Baltimore. 22\u201324 May 2018. Oral abstract 12.<br \/>\n<\/span><a href=\"http:\/\/regist2.virology-education.com\/presentations\/2018\/Antiviralpk\/29_patel.pdf\" rel=\"noopener\">http:\/\/regist2.virology-education.com\/presentations\/2018\/Antiviralpk\/29_patel.pdf<\/a> (PDF)<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Polly Clayden, HIV i-Base Rifabutin (RBT) can be given with oral cabotegravir (CAB) without dose adjustment, according to data presented at the 19th International Workshop on Clinical Pharmacology. A modest decrease in plasma CAB following long-acting (LA) administration with RBT &hellip;<\/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],"tags":[254],"class_list":["post-34379","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-pk-and-drug-interactions","tag-pk-workshop-2018"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/34379","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=34379"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/34379\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=34379"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=34379"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=34379"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}