Titre du document / Document title

Pharmacoepidemiologic investigation of clonazepam relative clearance by mixed-effect modeling using routine clinical pharmacokinetic data in Japanese patients

Auteur(s) / Author(s)

YUKAWA Eiji ⁽¹⁾ ; SATOU Masayasu ⁽¹⁾ ; NONAKA Toshiharu ⁽²⁾ ; YUKAWA Miho ⁽³⁾ ; OHDO Shigehiro ⁽¹⁾ ; HIGUCHI Shun ⁽¹⁾ ; KURODA Takeshi ⁽²⁾ ; GOTO Yoshinobu ⁽³⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Laboratory of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, JAPON
⁽²⁾ Department of Pharmacy, Fukuoka University Hospital, JAPON
⁽³⁾ Faculty of Pharmaceutical Sciences, Fukuoko University, JAPON

Résumé / Abstract

The effects of drug-drug interactions on clonazepam clearance were examined through a retrospective analysis of serum concentration data from pediatric and adult epileptic patients. Patients received clonazepam as monotherapy or in combination with other antiepileptic drugs. A total of 259 serum clonazepam concentrations gathered from 137 patients were used in a population analysis of drug-drug interactions on clonazepam clearance. Data were analyzed using a nonlinear 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 of clonazepam and one antiepileptic drug (carbamazepine or valproic acid), and 2.12. TBW^-0.119 for those patients receiving concomitant administration of clonazepam and more than two antiepileptic drugs. Clonazepam clearance decreased in a weight-related fashion in children, with minimal changes observed in adults. Concomitant administration of clonazepam and carbamazepine resulted in a 22% increase in clonazepam clearance. Concomitant administration of clonazepam and valproic acid resulted in a 12% increase in clonazepam clearance. Concomitant administration of clonazepam with two or more antiepileptic drugs resulted in a 23% to 75% increase in clonazepam clearance.

Revue / Journal Title

Journal of clinical pharmacology   ISSN 0091-2700   CODEN JCPCBR 

Source / Source

2002, vol. 42, n^o1, pp. 81-88 (28 ref.)

Langue / Language

Anglais

Editeur / Publisher

Sage Science, Thousand Oaks, CA, ETATS-UNIS  (1973) (Revue)

Mots-clés anglais / English Keywords

Cerebral disorder ; Central nervous system disease ; Nervous system diseases ; Enzyme inducer ; Benzodiazepine derivatives ; Metabolism ; Drug interaction ; Epidemiology ; Models ; Mongoloid ; Retrospective ; Elimination ; Distribution ; Absorption ; Human ; Pharmacokinetics ; Epilepsy ; Treatment ; Chemotherapy ; Anticonvulsant ; Clonazepam ;

Mots-clés français / French Keywords

Encéphale pathologie ; Système nerveux central pathologie ; Système nerveux pathologie ; Inducteur enzyme ; Benzodiazépine dérivé ; Métabolisme ; Interaction médicamenteuse ; Epidémiologie ; Modèle ; Mongoloïde ; Rétrospective ; Elimination ; Distribution ; Absorption ; Homme ; Pharmacocinétique ; Epilepsie ; Traitement ; Chimiothérapie ; Anticonvulsivant ; Clonazépam ;

Mots-clés espagnols / Spanish Keywords

Encéfalo patología ; Sistema nervosio central patología ; Sistema nervioso patología ; Inductor enzima ; Benzodiazepina derivado ; Metabolismo ; Interacción medicamentosa ; Epidemiología ; Modelo ; Mongoloide ; Retrospectiva ; Eliminación ; Distribución ; Absorción ; Hombre ; Farmacocinética ; Epilepsia ; Tratamiento ; Quimioterapia ; Anticonvulsivante ; Clonazepam ;

Localisation / Location

INIST-CNRS, Cote INIST : 10257, 35400009475121.0090