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Effects of renal function on recainam pharmacokinetics and pharmacodynamics
Author(s) -
Cheng Judy W. M.,
Charland Scott L.,
Goldfarb Stanley,
Spinler Sarah A.
Publication year - 1995
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/0009-9236(95)90033-0
Subject(s) - pharmacokinetics , renal function , cmax , pharmacodynamics , volume of distribution , medicine , elimination rate constant , urology , chemistry
Objectives 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 Clinical Research Center of the University of Pennsylvania Hospital. Twenty‐six volunteers participated in the study (group 1, glomerular filtration rate [GFR] <15 ml/min; group 2, GFR 15 to 50 ml/min; group 3, GFR >50 ml/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 area F, apparent clearance (CL/F), elimination rate constant (k e ), absorption rate constant (k a ), lag‐time (t lag ), time to peak (t max ), and maximum concentration (C max ) were determined with a least‐squares regression program. The relationship between recainam concentrations and electrocardiographic intervals were determined with the sigmoidal maximum effect model. Measured GFR was correlated to CLF with regression analysis. Results There were no significant differences found among groups in k a , t lag , t max , and V area F. Significant differences were found in CLF (114.4 ± 32.7, 319.4 ± 129.2, and 795.9 ± 341.8 ml/min, group 1 versus group 3 and group 2 versus group 3, p < 0.05), C max (3.54 ± 0.81, 1.77 ± 0.53, and 1.63 ± 0.66 μg/ml, group 1 versus group 2 and group 1 versus group 3, p < 0.01), and k e (0.074 ± 0.025, 0.137 ± 0.124, and 0.352 ± 0.300, group 1 versus group 3, p < 0.05). Recainam CLF was highly correlated with GFR ( r = 0.67, p = 0.001). Approximately 8.9% ± 3.8% of a recainam dose was eliminated 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 50 ) in group 1. Conclusion Recainam dosing adjustment is required in renal impairment. Recainam is not dialyzed to a significant extent. Further studies are required to fully characterize the pharmacodynamic profile of recainam. Clinical Pharmacology & Therapeutics (1995) 57 , 492–498; doi: