The pharmacokinetics of oral itraconazole in AIDS patients.
To test the hypothesis that absorption of orally administered itraconazole may be reduced in patients with the Acquired Immunodeficiency Syndrome (AIDS), 8 patients with AIDS were given two 100 mg capsules of itraconazole for 15 days. Plasma levels were measured by HPLC hourly for the first 8 h following ingestion, then at 24, 48, 72 and 96 h on days 1, 8 and 15. Peak plasma levels occurred after approximately 4 h. Mean peak plasma concentrations were 446 +/- 196 and 530 +/- 214 ng mL-1 at days 8 and 15. The area under the curve over 24 h (AUC0-24) was 2105 +/- 1241, 7679 +/- 3838 and 8748 +/- 4385 ng mL-1 h for days 1, 8 and 15, respectively. Steady-state was achieved after one week of dosing. There was no evidence of hepatotoxicity and one patient stopped itraconazole due to a rash. It may be concluded that the absorption of oral itraconazole capsules is reduced in AIDS patients, by a factor of approximately 50%, when compared with normal volunteers. AIDS patients may require higher doses of itraconazole than used in non-AIDS patients to achieve comparable plasma levels.
HIV/GUM Unit, St Stephen's Clinic and Westminister Hospital, London, UK.
D
D
Smith
V
V
van de Velde
R
R
Woestenborghs
B G
BG
Gazzard
D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism*; D000284:Administration, Oral; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D017964:Itraconazole; D007654:Ketoconazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged
D000935:Antifungal Agents; D017964:Itraconazole; D007654:Ketoconazole