Impact of cytochrome P450 inducers with or without inhibitors on the serum clobazam level in patients with antiepileptic polypharmacy

Purpose The aim of this study was to evaluate the effect of cytochrome P450 (CYP) inducers/inhibitors on the pharmacokinetics of clobazam (CLB) in patients receiving antiepileptic polypharmacy. Methods A total of 2,504 samples obtained from 1,280 patients for routine therapeutic drug monitoring were...

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Bibliographic Details
Published in:European journal of clinical pharmacology 2014-10, Vol.70 (10), p.1203-1210
Main Authors: Yamamoto, Yoshiaki, Takahashi, Yukitoshi, Imai, Katsumi, Takahashi, Masaaki, Nakai, Masahiko, Inoue, Yushi, Kagawa, Yoshiyuki
Format: Article
Language:English
Subjects:
Adolescent
Adult
Age Factors
Anticonvulsants - administration & dosage
Anticonvulsants - pharmacokinetics
Anticonvulsants - pharmacology
Benzodiazepines - administration & dosage
Benzodiazepines - pharmacokinetics
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Child
Child, Preschool
Cytochrome P-450 Enzyme Inducers - administration & dosage
Cytochrome P-450 Enzyme Inducers - pharmacology
Cytochrome P-450 Enzyme Inhibitors - administration & dosage
Cytochrome P-450 Enzyme Inhibitors - pharmacology
Dose-Response Relationship, Drug
Drug Interactions
Drug therapy
Drug Therapy, Combination
Epilepsy
Epilepsy - drug therapy
Female
Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy
Humans
Male
Medical sciences
Nervous system (semeiology, syndromes)
Neurology
Pharmacokinetics and Disposition
Pharmacology
Pharmacology. Drug treatments
Pharmacology/Toxicology
Polypharmacy
Retrospective Studies
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Summary:Purpose The aim of this study was to evaluate the effect of cytochrome P450 (CYP) inducers/inhibitors on the pharmacokinetics of clobazam (CLB) in patients receiving antiepileptic polypharmacy. Methods A total of 2,504 samples obtained from 1,280 patients for routine therapeutic drug monitoring were retrospectively reviewed. These samples were grouped according to the antiepileptic drug regimens or age, and then the concentration to dose (CD) ratio (serum level (ng/ml) divided by dose (mg/kg)) of CLB was calculated for comparison. Results The mean CD ratio of CLB in adult patients using enzyme inducers (phenytoin (PHT), carbamazepine (CBZ), and phenobarbital (PB) alone or in combination) was 60.8 % lower than the ratio in patients without inducers. Among the inducers, patients using PHT had a significantly lower CD ratio than patients using PB or CBZ ( p  
ISSN:0031-6970
1432-1041
DOI:10.1007/s00228-014-1719-5