Food increases the bioavailability of acitretin.
Eighteen healthy male volunteers received 50 mg oral doses of acitretin on two occasions, according to a random crossover design. Acitretin was administered during a complete fast or following a moderate breakfast. Plasma samples were obtained at various times and the concentration of acitretin and its 13-cis isomeric metabolite (Ro 13-7652) were quantified by a specific HPLC assay. The AUC0-15 for acitretin was increased when administered with food for all subjects (except one) with a mean increase of 90% (from 1175 to 2249 ng/ml.hr). The maximum plasma concentration of acitretin (Cmax) was increased by 70% when administered with food (from 245 to 416 ng/ml), while the time to reach Cmax was unaffected. The ratio of AUC of Ro 13-7652 to acitretin was the same for both the fasted and fed conditions; therefore, the formation of metabolite was not influenced by concomitant ingestion of food. The presence of food increases the apparent bioavailability of acitretin. A likely mechanism behind this observation is an increase in acitretin solubility in addition to an increase in the lymphatic absorption and a prolonged residence time of the drug in the gastrointestinal tract.
McNamara
P J
PJ
College of Pharmacy, University of Kentucky, Lexington 40536.
Jewell
R C
RC
Jensen
B K
BK
Brindley
C J
CJ
D017255:Acitretin; D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D004032:Diet; D005502:Food; D006801:Humans; D008297:Male; D014212:Tretinoin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
D014212:Tretinoin; D017255:Acitretin