Pharmacokinetics of itraconazole (oral solution) in two groups of human immunodeficiency virus-infected adults with oral candidiasis

Abstract

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.

Drug‐Drug Interaction between Itraconazole and the Antiretroviral Drug Lopinavir/Ritonavir in an HIV‐1–Infected Patient with Disseminated Histoplasmosis

“…However, the concentrations of the parent compound, as well as the metabolite, were lower than reported in prior studies [8], suggesting that steady state concentrations might not have been achieved. Immediately after the start of lopinavir/ritonavir therapy, the concentrations of itraconazole remained at the same level, despite the dose reduction, whereas hydroxyitraconazole concentrations were significantly decreased ( figure 1B).…”

“…In our patient, hydroxyitraconazole levels exceeded itraconazole levels before the start of lopinavir/ritonavir therapy, at day 11 of itraconazole treatment (figure 1A), as described elsewhere [3,8,9]. However, the concentrations of the parent compound, as well as the metabolite, were lower than reported in prior studies [8], suggesting that steady state concentrations might not have been achieved.…”

Craniosynostosis due to premature closing of the sagittal suture

“…11 High concentrations have been detected in saliva for about eight hours after single dose of itraconazole oral solution. 17 In patients at high risk of IFI, such as those post-allogeneic stem cell transplantation procedures, who have severe mucositis or graft versus host disease (GVHD), manifesting as a wide range of upper gastrointestinal abnormalities, oral administration may be difficult and absorption may be reduced. 18 19 Frequent vomiting or difficulty in swallowing can further hamper absorption and the achievement adequate levels of drug.…”

Itraconazole trough concentrations in antifungal prophylaxis with six different dosing regimens using hydroxypropyl‐β‐cyclodextrin oral solution or coated‐pellet capsules

“…The apparent half‐life of hydroxy‐itraconazole is about 14 h [1]. Steady state concentrations are reached after 2 weeks in normal volunteers [5] and in patients infected with the human immunodeficiency virus (HIV) if no loading dose is given [7].…”