{"id":34381,"date":"2018-06-29T08:28:23","date_gmt":"2018-06-29T08:28:23","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=34381"},"modified":"2018-06-29T09:43:33","modified_gmt":"2018-06-29T09:43:33","slug":"boosted-darunavir-800100-mg-twice-daily-might-overcome-interaction-with-rifampicin","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/34381","title":{"rendered":"Boosted darunavir 800\/100 mg twice daily might overcome interaction with rifampicin"},"content":{"rendered":"<p class=\"HTBsubhead3authorcredit\"><strong><span lang=\"EN-US\">Polly Clayden, HIV i-Base<\/span><\/strong><\/p>\n<p class=\"HTBBODYFIRST\"><strong><span lang=\"EN-US\">Modelling study suggests darunavir\/ritonavir twice 800\/100 mg daily might be sufficient to overcome the interaction with rifampicin in HIV positive people co-infected with TB, according to data presented at the <\/span>19th International Workshop on Clinical Pharmacology.<\/strong><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Co-administration of rifampicin (RIF) and boosted darunavir (DRV) is contra-indicated due to significant pharmacokinetic (PK) interactions that can reduce the efficacy of DRV. <\/span><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">This study aimed to look at the effects of RIF on the PK of ritonavir (RTV)-boosted DRV (DRV\/r) and strategies to overcome the interaction. <\/span><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">The investigators implemented in vitro results in physiologically-based pharmacokinetic (PBPK) models to identify DRV regimens with the highest likelihood of successful clinical outcomes. <\/span><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">In vitro inhibition studies confirmed the potent inhibition of RTV of the metabolism of DRV (IC50 RTV: 14 nM), which was counteracted by the induction observed following RIF treatment (IC50 RTV: 46 nM). <\/span><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Simulated DRV\/r PK parameters accurately predicted values previously seen in clinical studies for DRV Cmax, AUC24h, and Ctrough of DRV\/r 800\/100 mg once daily. <\/span><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Addition of 600 mg RIF resulted in a significant decrease of DRV Cmax, AUC24h, and Ctrough in the various simulated regimens: DRV\/r 800\/100 mg once daily, 1600\/200 mg once daily DRV\/r and 800\/100 mg twice daily. <\/span><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">The study generated a framework of in vitro data aimed at supporting the development of accurate PBPK models for predicting the PK of DRV\/r as well as to predict potential drug-drug interaction following co-administration of RIF. <\/span><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Based on these findings, the investigators suggested changing the DRV\/r regimen from 800\/100 mg once daily to 800\/100 mg twice daily as the most promising regimen to counter the interaction of RIF 600 mg once daily in HIV positive people co-infected with TB.<\/span><\/p>\n<p class=\"HTBreference-noindent\"><span lang=\"EN-US\">Reference<\/span><\/p>\n<p class=\"HTBreference-noindent\"><span lang=\"EN-US\">Jacobs S et al. Predicted pharmacokinetic interactions of rifampicin with ritonavir-boosted darunavir. 19th International Workshop on Clinical Pharmacology. Poster abstract 37.\u00a0 <\/span><\/p>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">\u00a0<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Polly Clayden, HIV i-Base Modelling study suggests darunavir\/ritonavir twice 800\/100 mg daily might be sufficient to overcome the interaction with rifampicin in HIV positive people co-infected with TB, according to data presented at the 19th International Workshop on Clinical Pharmacology. &hellip;<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,34,37],"tags":[254],"class_list":["post-34381","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-pk-and-drug-interactions","category-tb-coinfection","tag-pk-workshop-2018"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/34381","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=34381"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/34381\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=34381"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=34381"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=34381"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}