The effects of food and dose on the oral systemic availability of itraconazole in healthy subjects.
We have studied the influence of food and dose (50, 100, 200 mg) on the oral systemic availability of the broad spectrum antifungal itraconazole and the pharmacokinetics after repeated dosing of 100 mg in six healthy volunteers. The relative systemic availability of itraconazole capsules compared with solution averaged 39.8% in the fasting state but 102% in the post-prandial state. Food did not significantly affect the tmax of the capsules. Itraconazole AUC at single doses of 50, 100, and 200 mg had a ratio of 0.3:1:2.7, and the steady-state AUC (0-24) after 15 days of 100 mg was five times the single-dose AUC. These findings suggest non-linear itraconazole pharmacokinetics in the range of therapeutically used doses. Furthermore, capsules should be given shortly after a meal to ensure optimal oral systemic availability.
Van Peer
A
A
Department of Drug Metabolism and Pharmacokinetics, Janssen Research Foundation, Beerse, Belgium.
Woestenborghs
R
R
Heykants
J
J
Gasparini
R
R
Gauwenbergh
G
G
D000284:Administration, Oral; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005502:Food; D006801:Humans; D017964:Itraconazole; D007654:Ketoconazole / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D011897:Random Allocation; D012016:Reference Values
D000935:Antifungal Agents; D017964:Itraconazole; D007654:Ketoconazole