{"id":4453,"date":"2009-08-23T10:50:37","date_gmt":"2009-08-23T09:50:37","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=4453"},"modified":"2013-08-16T13:10:45","modified_gmt":"2013-08-16T13:10:45","slug":"interactions-between-arvs-and-antimalarials-atovaquone-and-proguanil","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/4453","title":{"rendered":"Interactions between ARVs and antimalarials atovaquone and proguanil"},"content":{"rendered":"

Simon Collins, HIV i-Base<\/strong><\/p>\n

Van Luin and colleagues from Nijmegen presented results showing significantly lower levels of the common antimalarials atovaquone and proguanil, commonly used together as prophylaxis, in HIV-positive patients on HAART compared to HIV-negative controls.<\/strong><\/p>\n

Seven-day PK results from HIV-positive patients already on established HAART including efavirenz (n=19), lopinavir\/r (n=19) or atazanavir\/r (n=19) were compared to levels in 20 HIV-negative volunteers following single-dose atovaquone\/proguanil (250\/150mg), administered with a fat standardised breakfast. Patients who were negative for CYP2C19 defective *2 and *3 alleles, the key enzyme for proguanil metabolism, were excluded from the proguanil comparisons.<\/p>\n

PK parameters were significantly lower in HIV-positive patients (all p<0.05), and are detailed in Table 1. Efavirenz or lopinavir\/r resulted in considerably reduced levels suggesting increased dosing may be required. Atazanavir\/r considerably lowered proguanil compared to the HIV-negative group, but more modestly lowered atovaquone suggesting that this interaction may be managed with perfect adherence.<\/p>\n

Table 1. Mean [range] atovaquone and proguanil levels<\/strong><\/p>\n\n\n\n\n\n\n\n\n
<\/td>\nHIV-negative<\/td>\nefavirenz<\/td>\nlopinavir\/r<\/td>\natazanavir\/r<\/td>\n<\/tr>\n
Atovaquone<\/td>\n<\/tr>\n
AUC 0-t (h*mg\/L)<\/td>\n112.9 [43.3-250.1]<\/td>\n35.3 [12.5-91.8]<\/td>\n39.1 [6.3-137.0]<\/td>\n75.3 [22.6-146<\/td>\n<\/tr>\n
Cmax (mg\/L)<\/td>\n2.0 [0.44-4.0]<\/td>\n1.2 [0.39-2.8]<\/td>\n1.3 [0.40-3.0]<\/td>\n1.1 [0.54-2.2]<\/td>\n<\/tr>\n
Proguanil (in patients without CYP2C19* or -*3)<\/td>\n<\/tr>\n
AUC 0-t (h*mg\/L)<\/td>\n1.3 [0.40-10.3]<\/td>\n0.55 [0.12-1.8]<\/td>\n0.42 [0.12-1.8]<\/td>\n0.34 [0.10-0.63]<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Comment<\/h3>\n

An important problem with this study is the use of HIV-negative controls compared to HIV-positive patients, so the differences may have been due to differences in PK of antimalarials in HIV-positive people. These are interesting data, but the results need confirmation and cannot be regarded as definitive.<\/strong><\/p>\n

Reference:<\/p>\n

Van Luin M et al. Drug interactions between atovaquone\/proguanil and antiretroviral agents. 10th International Workshop on Clinical Pharmacology of HIV Therapy, 15-17 April 2009, Amsterdam. Oral poster O-19.<\/p>\n","protected":false},"excerpt":{"rendered":"

Simon Collins, HIV i-Base Van Luin and colleagues from Nijmegen presented results showing significantly lower levels of the common antimalarials atovaquone and proguanil, commonly used together as prophylaxis, in HIV-positive patients on HAART compared to HIV-negative controls. Seven-day PK results …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,34],"tags":[133],"class_list":["post-4453","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-pk-and-drug-interactions","tag-pk-workshop-10th-2009"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/4453","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=4453"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/4453\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=4453"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=4453"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=4453"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}