Examination of some factors responsible for a food‐induced increase in absorption of atovaquone.

Abstract

1. Atovaquone is a potent antiprotozoal slowly and irregularly absorbed after administration as tablets to fasting volunteers. A series of studies was performed to investigate the effects of food, bile and formulation on atovaquone absorption. 2. In 18 healthy male volunteers, a high‐fat breakfast administered 45 min before 500 mg atovaquone as tablets increased AUC by 3.3‐fold (95% CI 2.8‐4.0) and Cmax 5.3‐fold (4.3‐6.6) compared with fasting. 3. The absorption of atovaquone from tablets was examined in 12 healthy male volunteers after an overnight fast, following toast alone, toast with 28 g butter (LOFAT), or toast with 56 g butter (HIFAT). Compared with absorption when fasted, toast had no significant effect but LOFAT increased AUC 3.0‐fold (2.1‐4.2) and Cmax 3.9‐fold (2.6‐5.8). HIFAT increased AUC 3.9‐fold (2.7‐5.5) and Cmax 5.6‐fold (3.8‐8.4). 4. The absorption of atovaquone was examined in nine healthy fasting male volunteers from tablets, an aqueous suspension, and an oily solution/suspension in miglyol (fractionated coconut oil). Compared with tablets, AUC following the aqueous suspension was increased 1.7‐fold (1.0‐2.7) and Cmax 2.4‐fold (1.7‐ 3.5). Following miglyol, AUC was increased to the same extent but Cmax was only increased 1.8‐fold (1.2‐2.6). 5. Atovaquone absorption was examined in eight healthy fasting male volunteers following an i.v. infusion of cholecystokinin octapeptide (CCK‐OP) which decreased gallbladder volume by 82% (73%‐90%) on occasion 1 or saline on occasion 2. AUC(0,12) was increased following CCK‐OP by 1.6‐fold (1.1‐2.4) and Cmax by 1.5‐fold (0.98‐2.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclodextrin/poly(anhydride) nanoparticles as drug carriers for the oral delivery of atovaquone

“…As a control, pulverised atovaquone was homogeneously dispersed in an aqueous solution of methylcellulose. The resulting suspension showed a mean particle diameter of about 640 nm, which was smaller than particle sizes previously reported by other research groups (Rolan et al 1994;Dearn 2000;Dixon et al 1996).…”

“…Thus, it was demonstrated that, for both the tablet and suspension formulations, the atovaquone concentration in plasma is greater when the drug is administered with food (Rolan et al 1994;Dixon et al 1996). Overall, it has been calculated that food increases the bioavailability of atovaquone 1.4-fold over that achieved in a fasting state (Rolan et al 1994); although, this amount can be higher depending on the fat content of the meal (Nicolaides et al 1999). …”

“…tablet or suspension), this drug is irregularly absorbed and it shows a very poor bioavailability. However, absorption of ATO can be improved by the simultaneous intake of food (Hughes et al 1991;Rolan et al 1994). Thus, the oral bioavailability of atovaquone has been calculated to be about 23% in the fasted state and 47% in the fed state (GlaxoSmithKline 2010).…”

A randomized, double-blind, placebo-controlled field trial to determine the efficacy and safety of Malarone (atovaquone/proguanil) for the prophylaxis of malaria in Zambia.

“…Studies have shown that the ingestion of food increases the bioavailability of atovaquone 17 and consequently all treatment regimens were administered within 45 min of a small meal. Medication was taken under direct supervision of trained field workers and compliance was further confirmed by a tablet count.…”

Effect of Khat ( Catha edulis ) Use on the Bioavailability, Plasma Levels and Antimalarial Activity of Chloroquine

“…[1][2][3][4][5][6] Drug-food, drug-drug and drug-herb interactions are factors that can alter the pharmacokinetic activity of a drug; these interactions can occur during absorption, distribution, metabolism or excretion. 7 Catha edulis of the Celastraceae family, also known as khat, is a plant widely cultivated in East Africa (e.g.…”