ITRACONAZOLE SOLUTION - HIGHER SERUM DRUG CONCENTRATIONS AND BETTER CLINICAL-RESPONSE RATES THAN THE CAPSULE FORMULATION IN ACQUIRED-IMMUNODEFICIENCY-SYNDROME PATIENTS WITH CANDIDOSIS

Aims-To compare the serum concentrations of itraconazole and hydroxyit raconazole after treatment with intraconazole cyclodextrin solution an d itraconazole capsules in human immunodeficiency virus (HIV) positive patients with oral candidosis. Methods-The pharmacokinetics of itraco nazole and its active metabolite hydroxy-itraconazole were assessed on days 1 and 7 of therapy in aquired immunodeficiency syndrome (AIDS) p atients with oral candidosis taking either itraconazole solution or ca psules and the serum concentrations (measured by high performance liqu id chromatography) correlated with the clinical response to therapy. I n addition, the in vitro susceptibility of Candida spp isolates taken from patients at the start of the therapy was assessed. Results-Nine o f 16 patients treated with itraconazole capsules and eight of 15 treat ed with the solution responded to treatment. Three of the non-responde rs in each treatment group were infected with isolates resistant to it raconazole in vitro. Although with both preparations there was conside rable inter-patient variability in the maximum recorded serum concentr ations of itraconazole, they were significantly lower on day 1 and day 7 in those receiving capsules compared with those taking the solution . Patients unresponsive to therapy, but infected with susceptible isol ates, had significantly lower concentrations of itraconazole and hydro xyitraconazole levels on days 1 and 7 than patients responding to trea tment. However, patients infected with itraconazole resistant isolates (tested in vitro) failed to respond to treatment despite achieving si milar serum concentrations of itraconazole and hydroxy-itraconazole to the responsive patients. For patients with in vitro susceptible isola tes a serum itraconazole concentration of < 1000 ng/ml on day 7 was pr edictive of therapeutic failure (specificity 71%, sensitivity 100%). C onclusions-Itraconazole cyclodextrin solution achieves higher serum it raconazole and hydroxy-itraconazole concentrations than the capsule fo rmulation in AIDS patients, and this is associated with improved effic acy.