Detection of carbamazepine drug interaction by multiple peak approach screening using routine clinical pharmacokinetic data

Multiple peak approach screening was used to detect the effects of other antiepileptic drugs on the population estimates of relative clearance of carbamazepine. Routine clinical pharmacokinetic data (N = 1,010) collected from 466 patients receiving carbamazepine were analyzed according to a simple steady-state pharmacokinetic model with the use of NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data. NONMEM estimates indicated that carbamazepine clearance decreased nonlinearly with increasing total body weight (TBW) in the maturation process (over an age range of 5 months to 15 years) and increased nonlinearly with increasing daily dose (mg/kg) of carbamazepine. Concomitant administration of other antiepileptic drugs resulted in an increased in clearance of carbamazepine as follows: valproic acid alone (VPA), 7%; phenobarbital alone (PB), 16%; more than two antiepileptic drugs (POLY), 27%. Final regression model of relative clearance (Cl) for all data was: Cl (mL/hr/kg) = 64.9. TBW (kg)-0.336.DOSE (mg/kg/day)0.465 1.07VPA 1.16PB 1.27POLY.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				H. Zhou Population-based assessments of clinical drug-drug interactions: qualitative indices or quantitative measures? J. Clin. Pharmacol., November 1, 2006; 46(11): 1268 - 1289. [Abstract] [Full Text] [PDF]

				H. Zhou, P. R. Mayer, J. Wajdula, and S. Fatenejad Unaltered Etanercept Pharmacokinetics With Concurrent Methotrexate in Patients With Rheumatoid Arthritis J. Clin. Pharmacol., November 1, 2004; 44(11): 1235 - 1243. [Abstract] [Full Text] [PDF]