Distribution of oral ketoconazole to vaginal tissue

Abstract

Plasma samples and biopsies of vaginal tissue were obtained from 23 healthy women undergoing operative sterilization, 1 to 6 h after a single oral dose of ketoconazole 200 mg. Drug concentrations in plasma and tissue, were measured by a specific gas chromatographic method. The vaginal tissue concentration averaged 2.4 times less than the corresponding plasma levels. Equilibrium between tissue, and plasma was established within 1 h after dosing, when vaginal tissue levels exceeded 1 microgram/g. Ketoconazole concentrations decayed monoexponentially over the time interval studied (1-6h), with the similar half-lives of 1.2 and 1.4 H in plasma and tissue, respectively. Following an oral 200 mg dose, a tissue concentration not less than 0.01 microgram/ml was maintained over a 12 h period. This concentration has been shown to prevent outgrowth of the invasive (pseudo) mycelial form of Candida albicans. Hence, a b.i.d. or t.i.d. dosage schedule of ketoconazole in vaginal candidosis would give continuously effective levels at the site of infection. Ketoconazole concentrations in vaginal fluid are thought to be much higher than in the tissue because of ion-trapping. The present data may explain the efficacy of oral ketoconazole in the treatment of vaginal candidosis.

Evaluation of a CGC-FID method for qualitative and quantitative analysis of azole antifungal drugs

“…There are, however, a few publications describing gas chromatographic analysis. Bifonazole and econazole have been analysed by GC-FID [9], clotrimazole by CGC with mass spectrometric de-tection (MSD) [10], ketoconazole by CGC with electron-capture detection (ECD) [11], and miconazole by GC with packed columns [12,13]. Fluconazole, a triazole derivative, has been analysed by CGC with a variety of detection methods -flame ionization detection (FID) [14], mass spectrometry (MS) [14,15], nitrogen-phosphorus detection (NPD) [16,17], and ECD [18,19].…”