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Examination of some factors responsible for a food‐induced increase in absorption of atovaquone.
Author(s) -
Rolan PE,
Mercer AJ,
Weatherley BC,
Holdich T,
Meire H,
Peck RW,
Ridout G,
Posner J
Publication year - 1994
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1994.tb04232.x
Subject(s) - atovaquone , absorption (acoustics) , medicine , environmental health , pharmacology , food science , chemistry , immunology , materials science , plasmodium falciparum , malaria , composite material
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)