Persistence of atovaquone in human sera following treatment: inhibition of Plasmodium falciparum development in vivo and in vitro.

摘要: Published pharmacokinetic data indicate that after treatment of patients with therapeutic doses atovaquone/proguanil hydrochloride (Malarone, GlaxoSmithKline Research Triangle Park, NC), the plasma half-lives these drugs are 70h and 15h, respectively. However, using two biologic assays (mosquito transmission in vitro asexual stage development), we demonstrate here sera from volunteers treated retained activity against Plasmodium falciparum up to 6 weeks such treatment. This was due atovaquone, as administration this drug alone replicated obtained combination. Most notably, development an atovaquone-resistant strain (NGATV01) P. not inhibited by taken atovaquone These for assays, though quantitative, more sensitive than usual physicochemical assays. Also, persistence at low concentrations long periods may increase risk resistant parasites arising.