Population pharmacokinetics of intravenous valproic acid in Korean patients.
OBJECTIVE
To determine population-based pharmacokinetic parameters for intravenous valproic acid, and the factors influencing these parameters, in Korean adults.


METHODS
Valproic acid concentrations were obtained using a peak and trough sampling scheme for 102 Korean epileptic patients who were not taking concurrent antiepileptic medication. Three hundred and fifty-four serum concentrations were analysed according to a one-compartment model with a mixed effect modelling method (NONMEM Ver 5.0). The influence of body-weight (kg), height, daily valproic acid dose (mg/day), body mass index (kg/m2), sex, and age on volume of distribution (Vd) and clearance (CL) was assessed in the course of analysis.


RESULTS
Vd and CL of valproic acid increased with body-weight. No significant influence of the other screened covariates was observed. The final regression model was: [equation: see text]. Interindividual variabilities (coefficient of variation) for CL and Vd were 32 and 18%, respectively. Residual error including intraindividual variability was 26.7%.


CONCLUSIONS
The current results may be used as a basic reference to optimize drug therapy with intravenous valproic acid. Further research on the paediatric population is necessary to confirm the non-linearity of the relation between body-weight and Vd.
Park
H-M
HM
Department of Neurology, Ghil Medical Center, Gachon Medical School, Korea.
Kang
S-S
SS
Lee
Y-B
YB
Shin
D-J
DJ
Kim
O-N
ON
Lee
S-B
SB
Yim
D-S
DS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D044466:Asian People; D001499:Bayes Theorem; D015992:Body Mass Index; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007723:Korea; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D014635:Valproic Acid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000927:Anticonvulsants; D014635:Valproic Acid