| Autor: |
Yukawa, Eiji, Satou, Masayasu, Nonaka, Toshiharu, Yukawa, Miho, Ohdo, Shigehiro, Higuchi, Shun, Kuroda, Takeshi, Goto, Yoshinobu |
| Zdroj: |
Journal of Clinical Pharmacology; Jan2002, Vol. 42 Issue 1, p81-88, 8p |
| Abstrakt: |
The effects of drug-drug interactions on clonazepam clearance were examined through a retrospective analysis ofse rum concentration data from pediatric and adult epileptic patients. Patients received clonazepam as monotherapy or in combination with other antiepileptic drugs. A total of259 serum clonazepam concentrations gathered from 137 patients were used in a population analysis ofdrug-drug interactions on clonazepam clearance. Data were analyzed using a non-linear mixed-effects modeling (NONMEM) technique. The final model describing clonazepam clearance was CL = 152 • TBW–0.181• DIF, where CL is clearance (ml/kg/h), TBW is total body weight (kg), and DIF (drug interaction factor) is a scaling factor for concomitant medication with a value of 1 for patients on clonazepam monotherapy, 1.18 for those patients receiving concomitant administration ofclonazepam and one antiepileptic drug (carbamazepine or valproic acid), and 2.12 • TBW -0.119 for those patients receiving concomitant administration ofclonazepam and more than two antiepileptic drugs. Clonazepam clearance decreased in a weight-related fashion in children, with minimal changes observed in adults. Concomitant administration ofclonazepam and carbamazepine resulted in a 22% increase in clonazepam clearance. Concomitant administration ofclonazepam and valproic acid resulted in a 12% increase in clonazepam clearance. Concomitant administration ofclonazepam with two or more antiepileptic drugs resulted in a 23% to 75% increase in clonazepam clearance. [ABSTRACT FROM PUBLISHER] |
| Databáze: |
Complementary Index |
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