{"id":7789,"date":"2010-02-08T00:15:30","date_gmt":"2010-02-08T00:15:30","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=7789"},"modified":"2013-08-06T07:24:21","modified_gmt":"2013-08-06T07:24:21","slug":"significant-interactions-between-tipranavirritonavir-and-statins","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/7789","title":{"rendered":"Significant interactions between tipranavir\/ritonavir and statins"},"content":{"rendered":"<p><strong>www.hiv-druginteractions.org<\/strong><\/p>\n<p><strong>Data from lopinavir\/ritonavir and rosuvastatin have shown that it is difficult to predict interactions between boosted protease inhibitors and statins.<\/strong><\/p>\n<p>Since tipranavir\/ritonavir has a net inhibitory effect on CYP3A4, it has the potential to increase atorvastatin concentrations. However, rosuvastatin is\u00a0considered unlikely to interact with tipranavir\/ritonavir since it is not a CYP3A4 substrate and is not extensively metabolised.<\/p>\n<p>Two open-label, prospective, single-arm, two-period studies, were performed in HIV-negative volunteers. These studies looked to identify interactions\u00a0between tipranavir\/ritonavir (500\/200 mg twice daily) and either rosuvastatin (10 mg single dose) or atorvastatin (40 mg single dose),<\/p>\n<p>Coadministration increased rosuvastatin AUC by 37% and increased Cmax by 2.23-fold. Atorvastatin AUC was increased by 9.36-fold and Cmax increased by\u00a08.61-fold, when coadministered. Tipranavir pharmacokinetic parameters were not affected by single-dose rosuvastatin or atorvastatin. The atorvastatin data\u00a0are consistent with marked inhibition of CYP3A4 and some transport proteins. The rosuvastatin data are consistent with previous findings evaluating this\u00a0interaction with lopinavir\/ritonavir and most likely due to inhibition of OATP1B1 and BCRP.<\/p>\n<p>Based on these interactions, the authors recommend low initial doses of rosuvastatin (5 mg) and atorvastatin (10 mg), with careful clinical monitoring of\u00a0rosuvastatin- or atorvastatin-related adverse events when combined with tipranavir\/ritonavir.<\/p>\n<p><strong>COMMENT<\/strong><\/p>\n<p><strong>Although these studies have shown the nature and magnitude of the pharmacokinetic interaction, they do not give any information on the\u00a0pharmacodynamic interaction (i.e. the cholesterol-lowering efficacy of each statin) when given with tipranavir\/ritonavir.<\/strong><\/p>\n<p><strong>Data from rosuvastatin\/lopinavir\/ritonavir have shown that although plasma concentrations of rosuvastatin were increased, the cholesterol lowering\u00a0efficacy was decreased when given in combination.<\/strong><\/p>\n<p>Source: <a href=\"http:\/\/www.hiv-druginteractions.org\">www.hiv-druginteractions.org<\/a> (23 November 2009).<\/p>\n<p>Ref: Pham PA et al. Differential effects of tipranavir plus ritonavir on atorvastatin or rosuvastatin pharmacokinetics in healthy volunteers. Antimicrob Agents Chemother, 2009, 53(10): 4385-4392.<br \/>\n<a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19667285\">http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19667285<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>www.hiv-druginteractions.org Data from lopinavir\/ritonavir and rosuvastatin have shown that it is difficult to predict interactions between boosted protease inhibitors and statins. Since tipranavir\/ritonavir has a net inhibitory effect on CYP3A4, it has the potential to increase atorvastatin concentrations. However, rosuvastatin &hellip;<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[34],"tags":[],"class_list":["post-7789","post","type-post","status-publish","format-standard","hentry","category-pk-and-drug-interactions"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/7789","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\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=7789"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/7789\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=7789"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=7789"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=7789"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}