Effects of renal function on recainam pharmacokinetics and pharmacodynamics
Object&es: To investigate the pharmacokinetics and pharmacodynamics of recainam, an investigational class I antiarrhythmic agent, in subjects with various degrees of renal function. Methods: This single-dose open-label study was carried out at the Ciinicai Research Center of the University of Pennsylvania Hospital. Twenty-six volunteers participated in the study (group 1, glomerular filtration rate [GFR] <15 mi/min; group 2, GFR 15 to 50 ml/nun; group 3, GPR >50 mI/min). After a single 400 mg oral dose, plasma samples were collected for the following 48 hours. Recainam pharmacokinetic parameters of apparent volume of distribution (V ,,/&), apparent clearance (CL/F), elimination rate constant (kJ, absorption rate constant (k& lag-time (t,,), time to peak (t-J, and maximum concentration (C,,,d were determined with a least-squares regression program. The relationship between recainam concentrations and electrocardiographic intervals were determined with the sigmoidai maximum effect model. Measured GPR was correlated to CIJF with regression analysis. Results: There were no significant differences found among groups in k, tlas, f,, and V-IF. Signiticant differences were found in CL/P (114.4 + 32.7,319.4 + 129.2, and 795.9 2 341.8 ml/nun, group 1 versus group 3 and group 2 versus group 3,p < 0.05), C, (3.54 A 0.81, 1.77 + 0.53, and 1.63 + 0.66 @ml, group 1 versus group 2 and group 1 versus group 3, p < O.Ol), and k, (0.074 f 0.025, 0.137 f 0.124, and 0.352 + 0.300, group 1 versus group 3, p < 0.05). Recainam CID was highly correlated with GFR (r = 0.67, p = 0.001). Approximately 8.9% + 3.8% of a recainam dose was eiiminated during a 4-hour hemodialysis period. There was a trend (but not statistically significant) of increasing maximum percentage change in PR interval and the effective recainam concentration that produces half of its maximum effect (EC,,) in group 1. Cmlh:
Recainam dosing adjustment is required in renal impairment. Recainam is not diaiyxed to a sign&ant extent. Further studies are required to t?tlly characterize the pharmacodynamic profile of recainam.