Population Pharmacokinetics of Carbamazepine in Adults with Epilepsy

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Abstract

Study Objective.

To conduct a population pharmacokinetic analysis of carbamazepine (CBZ).

Design.

Retrospective chart review.

Setting.

Ambulatory neurology clinics at three medical centers.

Patients.

Patients diagnosed with epilepsy from 1991-1995. The index set included 829 adults receiving CBZ. A separate validation set consisted of 50 patients.

Interventions.

None.

Measurements and Main Results.

Final regression equations were apparent oral clearance (Cl/F) (L/hr) = (0.0134 • TBW + 3.58), •1.42 if receiving phenytoin only; •1.17 if receiving phenobarbital or felbamate; •1.62 if receiving phenytoin and phenobarbital or felbamate; •0.749 if age >70 years; apparent volume of distribution (Vd/F) (L) = 1.97 •total body weight; absorption rate constant (hr-1) = 0.441. Interindividual variability in Cl/F and Vd/F was 26% and 82%, respectively. Residual variability was 1.8 mg/L. Predictive performance analysis of the validation set provided a mean prediction error of 0.6 mg/L and median absolute error of 2.4 mg/L.

Conclusions.

These routinely collected data provided quantitative estimates of changes in CBZ Cl/F due to comedication and an age-related decrease in Cl/E The derived regression equations reasonably predicted concentrations in a separate validation set.

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