Plasma and Saliva Propafenone Concentrations at Steady State

Abstract

Twenty-four healthy male subjects were administered 300mg of propafenone every 8h for 6 d in each of two phases that were separated by 2 d. Plasma samples were collected during the approach to steady state for each phase, and plasma and saliva samples were collected frequently at steady state. Both plasma and saliva propafenone were assayed by a specific HPLC method. Two estimates of elimination half-life (l1/2), mean steady-state concentration (CPSS¯), time to maximal concentration (tmax), and maximal concentration (CPmax), were estimated for each subject. Also mean steady-state saliva concentrations (CSSS¯), time to maximal saliva concentration (tSmax), and maximal saliva concentrations (CSmax) were estimated. A large inter subject variance in both t1/2 and CPSS¯ were observed in the 24 subjects, with the t1/2 values ranging from 2.1 to 27.2h and the CPSS¯ values from 0.3 to 3.03 μg/mL. Each subject was quite consistent for the two phases, suggesting a relatively low intrasubject variance for propafenone kinetics. A histogram shows most subjects to have t1/2 values between 2 and 10 h, with diminishing numbers of subjects at greater t1/2 values rather than a bimodal distribution. Saliva concentrations ranged from 12 to 72% of the corresponding plasma concentrations, being 24.7 ± 11.1% of the simultaneously collected plasma sample overall (mean ± SD). A significant (p<0.001) positive correlation exists between CPSS¯ and CSSS¯.