Population pharmacokinetics of carbamazepine in adults with epilepsy

Pharmacotherapy. 1998 Mar-Apr;18(2):273-81.

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 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / pharmacokinetics*
  • Anticonvulsants / therapeutic use
  • Biological Availability
  • Body Weight
  • Carbamazepine / administration & dosage
  • Carbamazepine / blood
  • Carbamazepine / pharmacokinetics*
  • Drug Therapy, Combination
  • Epilepsy / drug therapy*
  • Evaluation Studies as Topic
  • Felbamate
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Phenobarbital / therapeutic use
  • Phenylcarbamates
  • Phenytoin / therapeutic use
  • Predictive Value of Tests
  • Propylene Glycols / therapeutic use
  • Regression Analysis
  • Retrospective Studies
  • Time Factors

Substances

  • Anticonvulsants
  • Phenylcarbamates
  • Propylene Glycols
  • Carbamazepine
  • Phenytoin
  • Felbamate
  • Phenobarbital