TY - JOUR T1 - Pharmacokinetics of disopyramide in the dog. Importance of mono-N-dealkylated metabolite kinetics in assessing pharmacokinetic modeling of the parent drug. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 42 LP - 49 VL - 18 IS - 1 AU - C S Cook AU - P R Gwilt AU - K Kowalski AU - S Gupta AU - J Oppermann AU - A Karim Y1 - 1990/01/01 UR - http://dmd.aspetjournals.org/content/18/1/42.abstract N2 - The antiarrhythmic drug disopyramide (DP) is metabolized to the mono-N-dealkylated compound (MND) and to the pyrrolidone derivative (PYR). This study examines the detailed pharmacokinetic characteristics of DP and MND when given simultaneously or separately to dogs. DP and MND were both relatively well absorbed and showed similar pharmacokinetic characteristics. However, the amount of PYR relative to MND as judged by the area under the plasma concentration-time curves (AUC) following oral or iv administration was much greater with DP than with MND. These findings were also supported by the urinary excretion values where the PYR/MND ratio with DP was much greater than with the MND administration. For an explanation of this phenomenon, plasma concentration-time curves for DP, MND, and PYR were simultaneously analyzed assuming various pharmacokinetic models. The plasma levels of these compounds were best described when nonlinear kinetics were assumed for conversion of MND to PYR. ER -