Effect of CYP2C19 polymorphisms on stiripentol administration in Japanese cases of Dravet syndrome.

Abstract

OBJECTIVE:

The objective of this study was to investigate stiripentol (STP) administration in cases of Dravet syndrome (DS) by comparing CYP2C19 allelic polymorphisms with the clinical effects of STP, including plasma concentrations of concomitant drugs and adverse effects of STP.

MATERIALS AND METHODS:

Eleven cases of DS cases were included. Demographic and clinical characteristics of the cases (age at the study period, body weight, mean dose and plasma concentration of valproate acid (VPA)/clobazam (CLB) off and on STP, mean plasma concentration of norclobazam (N-CLB) off and on STP, degree of seizure reduction, and adverse effects of STP) were examined with each CYP2C19 polymorphism.

RESULTS:

There were 3 cases of DS with wild type, 6 with intermediate type, and 2 with poor type of CYP2C19 polymorphisms. The N-CLB concentration/CLB dose ratio and N-CLB/CLB concentration ratio off STP were significantly higher in poor metabolizers. Three (37%) of 8 cases showed no effectiveness of STP regardless of the N-CLB concentration increase, and 1 (33%) of 3 cases showed effectiveness of STP regardless of N-CLB concentration decrease. In total, 6 (54%) of 11 cases with DS had >50% reduction in seizure frequency without significant differences in CYP2C19 polymorphisms.

CONCLUSION:

This study demonstrated an effect of CYP2C19 polymorphisms on STP administration in Japanese cases of DS. There were cases of seizure reduction regardless of N-CLB concentration decrease on STP, which suggests a significant anti-convulsant action of STP. N-CLB concentration decrease on STP was observed in 1 case with ketogenic diet and 2 cases with (∗)3 allelic polymorphisms of CYP2C19.

• Authors: Takeshi Kouga, Hiroko Shimbo, Mizue Iai, Sumimasa Yamashita, Atsushi Ishii, Yukiko Ihara, Shinichi Hirose, Kazuhiro Yamakawa, Hitoshi Osaka
• Journal: Brain & development (Brain Dev) Vol. 37 Issue 2 Pg. 243-9 (Feb 2015) ISSN: 1872-7131 [Electronic] Netherlands
• PMID: 24819914 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Anticonvulsants
• Dioxolanes
• Cytochrome P-450 CYP2C19
• stiripentol

Topics

• Adolescent
• Anticonvulsants (therapeutic use)
• Asian People (genetics)
• Child
• Child, Preschool
• Cytochrome P-450 CYP2C19 (genetics)
• Dioxolanes (therapeutic use)
• Epilepsies, Myoclonic (drug therapy, genetics)
• Female
• Humans
• Infant
• Male
• Pharmacogenetics
• Polymorphism, Single Nucleotide (genetics)
• Retrospective Studies