The pharmacokinetics of
itraconazole formulated in a
hydroxypropyl-beta-cyclodextrin oral
solution was determined for two groups of human immunodeficiency virus (HIV)-infected adults with
oral candidiasis (group A, 12 patients with CD4+ T-cell count of >200/mm3 and no
AIDS, and group B, 11 patients with CD4+ T-cell count of <100/mm3 and
AIDS). Patients received 100 mg of
itraconazole every 12 h for 14 days. Concentrations of
itraconazole and
hydroxyitraconazole, the main active metabolite, were measured in plasma and saliva by high-performance liquid chromatography. Pharmacokinetic parameters determined at days 1 and 14 (the area under the concentration-time curve from 0 to 10 h, the maximum concentration of
drug in plasma [Cmax], and the time to Cmax) were comparable in both groups. Trough levels in plasma (Cmin) were similar in both groups for the complete duration of the study. An effective concentration of
itraconazole in plasma (>250 ng/ml) was reached at day 4. At day 14, Cmin values of
itraconazole were 643 +/- 304 and 592 +/- 401 ng/ml for groups A and B, respectively, and Cmin values of
hydroxyitraconazole were 1,411 +/- 594 and 1,389 +/- 804 ng/ml for groups A and B, respectively. In saliva, only unchanged
itraconazole was detected, and mean concentrations were still high (>250 ng/ml) 4 h after the intake, which may contribute to the fast clinical response. In conclusion, the oral
solution of
itraconazole generates effective levels in plasma and saliva in HIV-infected patients; its relative bioavailability is not modified by the stage of
HIV infection.