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.


METHODS
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.


CONCLUSIONS
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.
Laboratory of Evidence-Based Pharmacotherapy, College of Pharmaceutical Sciences, Daiichi University, Fukuoka, Japan. yukawa@daiichi-cps.ac.jp
E
E
Yukawa
K
K
Orio
M
M
Yukawa
K
K
Terao
H
H
Kinoshita
D000042:Absorption; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics*; D003625:Data Collection; D004206:Disopyramide / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D015203:Reproducibility of Results
D000889:Anti-Arrhythmia Agents; D004206:Disopyramide