"COMPARISON OF CARBAMAZEPINE CLEARANCE BETWEEN EPILEPTIC PATIENTS AND PATIENTS WITH ACUTE MANIA"

Abstract

The purpose of this study was to assess the influence of acute manic phase on the steady state
pharmacokinetics of carbamazepine (CBZ) in bipolar patients. Forty one acutely manic andd 76 epileptic
patients entered thispprospective study. CBZ apparent oral clearance (CL/F) values were calculated in
both groups and were compared with each other. CBZ clearance is affected by different factors such as
age, body weight, dosage and the use of concurrent medications. However, since these factors were
similar between the two groups, our results could not be affected by these confounding factors.
Comparison between epileptic and manic patients showed that CL/F values in acutely manic patients
were significantly higher than epileptic patients (0.128 ± 0.016 vs. 0.112 ± 0.0147 L/hr/kg, p< 0.0001).
As a result, acutely manic patients require more CBZ dosages to achieve serum concentrations
comparable with those found in epileptic patients. Increased CBZ clearance in acutely manic patients may
be related to increase of catecholamine and sympathetic activity in these patients. This results in increased
hepatic blood flow which may affect the hepatic clearance of drug. Besides, due to the abnormalities in
membrane transport of acutely manic patients, it may be suggested that cellular uptake of the drug and its
volume of distribution may be affected. Since our study is a preliminary investigation in this field, further
detailed pharmacokinetic study in acutely manic patients are warranted to confirm results of this study.