ABSORPTION AND EXCRETION OF RADIOACTIVITY AFTER INTRAVAGINAL ADMINISTRATION OF AN ADVANCED DELIVERY SYSTEM OF C-14-FLUTRIMAZOLE VAGINAL CREAM TO POSTMENOPAUSAL WOMEN

In order to improve the effectiveness of treatment of vaginal yeast in fections, flutrimazole, (CAS 119006-77-8), a broad spectrum local imid azolic fungicide, has been formulated in an advanced delivery system ( Site Release(R), here in after briefly referred to as SR) designed to improve vaginal retention of the drug. To determine the extent of abso rption of C-14-flutrimazole from this formulation, the absorption and excretion of total radioactivity have been studied in healthy postmeno pausal female volunteers after intravaginal administration of approxim ately 5 g of SR Vaginal Cream containing 2% C-14-flutrimazole. Concent rations of unchanged flutrimazole have also been measured in plasma an d urine, using a validated gas chromatography-mass spectrometry method . The rate of absorption was slow, with a mean peak plasma radioactivi ty concentration, C-max, of 56 ng equivalents/ml, achieved at a mean T -max of 28 h. Corresponding parameters for flutrimazole were 1.94 ng/m l 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 flut rimazole were eliminated from plasma with terminal half-lives of 37 an d 22 h, respectively. From the proportion of the radioactive dose excr eted in urine and faeces, the maximal extent of absorption indicated f or the intravaginal dose was about 8%, which is similar to that observ ed with other imidazolic compounds administered by this route. Thus, t he formulation achieves the aim of prolonged drug action through the m aintenance of therapeutic concentrations of the drug at the site of in fection without notably increased absorption.