Population pharmacokinetics of steady-state carbamazepine in Egyptian epilepsy patients

Journal of Clinical Pharmacy and Therapeutics, 05/08/2012

The population (POP) pharmacokinetic (PK) model the authors have developed for carbamazepine (CBZ) shows good predictive performance in Egyptian adult and pediatric patients with epilepsy. Another PK study to better define the effect of different covariates would improve on the model for dosage individualization.

Methods

  • Single steady-state (SS) trough plasma concentrations of CBZ were available for 302 patients with epilepsy (55.6% men and 44.4% women) who were categorized as children (n = 118) and adults (n = 184) with mean age (years) ± SD of 10.6 ± 4.8 and 29.4 ± 9.9, respectively.
  • Carbamazepine was given as an oral suspension (n = 19) or controlled release tablet (n = 283) with average dose of 15.0 ± 7.8 mg/kg per day.
  • A one-compartment model with first-order absorption and elimination for SS conditions (ADVAN2, SS2, TRANS2) was applied using NONMEM 6.2.
  • Separate absorption rate constants were modelled for the two formulations.
  • The mean POP CL, its intersubject variability (ISV), as well as residual error of CBZ concentration were estimated.

Results

  • The POP estimate for CL was 3.5 L/h with coefficient of variation value of 2.6%, which was consistent with literature data.
  • The ISV on CL was 44.5%.
  • The POP PK model was validated by bootstrap re-sampling, and the individual estimates were within the 95% CI of the bootstrap results.
  • Different covariates that might affect CBZ CL have been evaluated but the limited number of samples per individual prevented precise covariate analysis.

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