Arzneimittel-Forschung 1998-05-01

Absorption and excretion of radioactivity after intravaginal administration of an advanced delivery system of 14C-flutrimazole vaginal cream to postmenopausal women.

B John, S G Wood, J Ramis, I Izquierdo, J Forn

Index: Arzneimittelforschung 48(5) , 512-7, (1998)

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Abstract

In order to improve the effectiveness of treatment of vaginal yeast infections, flutrimazole, (CAS 119006-77-8), a broad spectrum local imidazolic fungicide, has been formulated in an advanced delivery system (Site Release, here in after briefly referred to as SR) designed to improve vaginal retention of the drug. To determine the extent of absorption of 14C-flutrimazole from this formulation, the absorption and excretion of total radioactivity have been studied in healthy postmenopausal female volunteers after intravaginal administration of approximately 5 g of SR Vaginal Cream containing 2% 14C-flutrimazole. Concentrations of unchanged flutrimazole have also been measured in plasma and urine, using a validated gas chromatography-mass spectrometry method. The rate of absorption was slow, with a mean peak plasma radioactivity concentration, Cmax, of 56 ng equivalents/ml, achieved at a mean Tmax of 28 h. Corresponding parameters for flutrimazole were 1.94 ng/ml at 24 h. At 24 h post-dose, unchanged flutrimazole represented only 3% of plasma total radioactivity which indicates that flutrimazole is extensively metabolised in man. Total radioactivity and unchanged flutrimazole were eliminated from plasma with terminal half-lives of 37 and 22 h, respectively. From the proportion of the radioactive dose excreted in urine and faeces, the maximal extent of absorption indicated for the intravaginal dose was about 8%, which is similar to that observed with other imidazolic compounds administered by this route. Thus, the formulation achieves the aim of prolonged drug action through the maintenance of therapeutic concentrations of the drug at the site of infection without notably increased absorption.