Estimation of population pharmacokinetics for carbamazepine in Malaysian patients using the OPT® computer program

Abstract

We used OPT to estimate individual and population pharmacokinetics for carbamazepine (CBZ) in Malaysian epileptic patients attending our Neurology Clinic. We noted that plasma CBZ concentrations and clearances correlated poorly with daily doses and body weights respectively but we found the values for clearance, volumes of distribution, elimination rate constants and half lives to be in good agreement with earlier reports. We conclude that OPT is a simple yet useful program to derive individual and population pharmacokinetic parameters for CBZ for use in dosage adjustments. We also conclude that although the Malaysian population do not differ substantially in handling CBZ, available data for the pharmacokinetic parameters must be used cautiously in applying it to the therapeutic drug monitoring for CBZ in our patients.

Population pharmacokinetic modeling of steady state clearance of carbamazepine and its epoxide metabolite from sparse routine clinical data

“…The result showed that the measurements by FPIA were 4·58 ± 6·64% higher than those obtained with HPLC and the cross‐reaction of CBZE decreased non‐linearly, from 61 to 27%, with increase in CBZE concentration. Therefore, the estimates from two studies were close and in agreement with the results of other studies in other populations (5–13).…”

“…When normalizing by the mean body weight for the patients, V/F for CBZ and CBZE were 1·37 and 3·34 L/kg, respectively. The estimate for CBZ was consistent with published values, which vary from 1·13 to 2·16 L/kg (5–14), whereas the estimate for CBZE was much higher than those reported 0·44 ∼1·18 L/kg (1, 30–33) under the unsteady‐state.…”

“…Data analysis was performed using the NONMEM NONMEM program (version V level 1.1, double precision) (NONMEM Project Group, San Francisco, CA, USA) coupled with Microsoft Fortran PowerStation 4.0. The concentration-time profiles of both CBZ and CBZE were described using a one-compartment model with first-order absorption and firstorder elimination according to the literature (1,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). The first-order estimation method was used and the estimates from the final model were confirmed using the first-order conditional estimation (FOCE) method with interaction.…”

“…There are several extensive population PK studies published on CBZ (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). However, except for the one performed in Australia (12) with part of the data derived from high performance liquid chromatography (HPLC) measurements, all of the published studies were based on immunoassay analysis of CBZ blood samples except.…”

Population Pharmacokinetics of Carbamazepine in Indian Epileptic Patients

“…The population pharmacokinetic parameters of phenytoin and carbamazepine in these populations were reported through different investigations (15)(16)(17)(18)(19)(20). There are no reports on population pharmacokinetic parameters of any of these drugs in the Indian population.…”