Urinary excretion kinetics of intact quinidine and 3-OH-quinidine after oral administration of a single oral dose of quinidine gluconate in the fasting and non-fasting state

Abstract

To obtain more precise urinary excretion data of intact quinidine (D) and its main metabolite, 3-OH-quinidine (DM), the specific HPLC method of Bonora et al has been used to follow its urinary excretion kinetics. In a cross-over study, 2 commercial dosage forms of quinidine gluconate, fast- and slow-release, were administered to 18 healthy subjects who had fasted for 10 hours in 3 treatments which were administered during the fasting period (T1), and before (T2) of after (T3) a standard breakfast. The urine was collected at fixed time intervals for 72 hours after the administration of a single dose (405 mg of quinidine base). The difference between the drug release characteristics of the two products was studied by analysing the cumulative amount of D and DM excreted as a function of time, and the time required to reach the maximum value for the urinary excretion rate of intact quinidine. A food effect could be noticed among treatments with the conventional fast-release dosage form when comparing the maximum values of the urinary excretion rate of D (T2 greater than T1). There was no significant difference in the percentage of drug absorbed from the 2 products, according to the data on the cumulative amount of D and DM. The parameters estimated for quinidine and the metabolite were: the apparent half-life of elimination, the urinary excretion rates and the time to reach a maximum value in the urinary excretion rate. The urinary excretion rate constant and the renal clearance were also quantified for quinidine by combining urinary parameters with the corresponding serum data previously reported.