HPLC method for pharmacokinetic studies on ciclopirox olamine in rabbits after intravenous and intravaginal administrations.

This paper reports a HPLC method to detect unchanged and glucuronide derivatives of ciclopirox olamine (a substituted 2-pyridone antimycotic) and gives pharmacokinetics in rabbits after i.v. and intravaginal administration. The HPLC method utilizes a RP 18 reverse phase column, a mobile phase of water and acetonitrile (60/40), a flux of 1 ml/min and wavelength of 304 nm. For the determination of free ciclopirox the plasma drug is methylated with dimethyl sulphate, extracted with n-exane, purified on Adsorbex CN and injected into the column. For the determination of total (free and glucuronide derivatives) ciclopirox the plasma is previously hydrolized with beta-glucuronidase before the application of the above procedure. In rabbits the drug is administered at 15 mg/kg for both routes; the t1/2 elim is 2.1 hours, the total clearance/F is 0.73 1.h-1 and the distribution volume/F is 2.2 1. Ciclopirox olamine, after intravaginal administration, shows low absorption (about 2%) and is mainly transformed into glucuronide derivatives.