Bioavailability of 11 quinidine formulations adn pharmacokinetic variation in humans

The bioavailabilities of eight quinidine sulfate, two gluconate, and one polygalacturonate formulations were compared, with one of the sulfate formulations as a reference (R) in a panel of 24 volunteers, according to a design comprising duplicate 6 x 6 Latin squares in two subject groups. Only one gluconate formulation (H) gave a significantly lower (p less than 0.05) area under the curve from 0 to 30 hr (AUC30), 90% or R, which was not as significant as AUC infinity (94% of R). Formulation H also gave a significantly lower peak concentration (Cmax) and a longer time to peak concentration (tmax) and generally exhibited some characteristics of sustained-release product. In addition, one product (F) gave a significantly higher Cmax while another formulation (D) gave a longer tmax. The wide range of dissolution times obtained with these products with three test conditions was not reflected in the AUC, Cmax, or tmax values obtained, except the Formulation H was consistently the slowest to dissolve. The terminal rate constants, expressed as t 1/2, of the 24 subjects gave an overall mean of 7.49 +/- 0.77 hr and ranged from 6.24 +/- 0.28 to 0.49 +/- 0.90 hr in individuals. The estimated total body clearance, with the assumption that the oral bioavailability was 70%, gave an overall mean of 4.22 +/- 1.05 and ranged from 2.49 +/- 0.28 to 6.42 +/- 0.70 mg/min/kg in individuals, demonstrating the wide range of quinidine disposition even in healthy subjects; this finding is in agreement with recently published results.