Population pharmacokinetic investigation of disopyramide by mixed effect modelling using routine clinical pharmacokinetic data in Japanese patients

OBJECTIVE: To estimate the population pharmacokinetic parameters of disopyramide using non-linear mixed effects modelling. METHOD: A total of 148 serum levels from 109 patients (61 males and 48 females) receiving disopyramide were collected. RESULTS: The final pharmacokinetic model was Cl (L/h)=3.75.TBW0.567.AGE-0.374.Conc(-0.719).1.48(DOSE>or=5), Vd (L/kg)=4.13 and k(a) (h-1)=0.363, where Cl is total body clearance, Vd is apparent volume of distribution, k(a) is absorption rate constant, TBW is total bodyweight (kg), AGE is age (years), Conc is the concentration of disopyramide (microg/mL), and DOSE>or=5=1 for patient received 5 mg/kg/day of disopyramide dosage or over and 0 otherwise. CONCLUSION: Application of the findings in this study to patient care may permit selection of an appropriate initial maintenance dosage to achieve target disopyramide concentrations and the desired therapeutic effect.