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Population Pharmacokinetics of Carbamazepine in Adults with Epilepsy
Author(s) -
Graves Nina M.,
Brundage Richard C.,
Wen Yandong,
Cascino Greg,
So Elson,
Ahman Peter,
Rarick John,
Krause Sandra,
Leppik Ilo E.
Publication year - 1998
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1998.tb03853.x
Subject(s) - carbamazepine , phenytoin , felbamate , medicine , anticonvulsant , epilepsy , population , volume of distribution , therapeutic drug monitoring , phenobarbital , pharmacokinetics , psychiatry , environmental health
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 (V d /F) (L) = 1.97 • total body weight; absorption rate constant (hr −1 ) = 0.441. Interindividual variability in Cl/F and V d /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.