Population pharmacokinetics of carbamazepine in adults with epilepsy.
OBJECTIVE
To conduct a population pharmacokinetic analysis of carbamazepine (CBZ).


METHODS
Retrospective chart review.


METHODS
Ambulatory neurology clinics at three medical centers.


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


METHODS
None.


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.
Graves
N M
NM
College of Pharmacy, University of Minnesota, Minneapolis 55455, USA.
Brundage
R C
RC
Wen
Y
Y
Cascino
G
G
So
E
E
Ahman
P
P
Rarick
J
J
Krause
S
S
Leppik
I E
IE
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D001835:Body Weight; D002220:Carbamazepine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy*; D005069:Evaluation Studies as Topic; D000078328:Felbamate; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010634:Phenobarbital / Q000627:therapeutic use; D048448:Phenylcarbamates; D010672:Phenytoin / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011409:Propylene Glycols / Q000627:therapeutic use; D012044:Regression Analysis; D012189:Retrospective Studies; D013997:Time Factors
D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D002220:Carbamazepine; D010672:Phenytoin; D000078328:Felbamate; D010634:Phenobarbital