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Population pharmacokinetics of carbamazepine in adults with epilepsy
N M Graves1, R C Brundage, Y Wen
1College of Pharmacy, University of Minnesota, Minneapolis 55455, USA.
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 x TBW + 3.58), x 1.42 if receiving phenytoin only; x 1.17 if receiving phenobarbital or felbamate; x 1.62 if receiving phenytoin and phenobarbital or felbamate; x 0.749 if age > or = 70 years; apparent volume of distribution (Vd/F) (L) = 1.97 x 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/F The derived regression equations reasonably predicted concentrations in a separate validation set.
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