The clinical impact of cytochrome P450 polymorphisms on anti-epileptic drug therapy

Saruwatari, Junji; Ishitsu, Takateru; Shioiri, Takayuki; Shimomasuda, Masatsugu; Okada, Yusuke; Goto, Shuji; Nagata, Rie; Takashima, Ayaka; Yoshida, Shizuo; Yoshida, Shuichi; Yasui‐Furukori, Norio; Kaneko, Sunao; Nakagawa, Kazuko

doi:10.3805/eands.3.34

Cited by 8 publications

(24 citation statements)

References 62 publications

(108 reference statements)

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“…We verified the clinical impact of the CYP2C19 genotype on the effects of zonisamide therapy in 99 Japanese patients as cited above [12]. The median concentration to dose ratios of zonisamide in PMs tended to be higher than in homo EMs [12].…”

Section: Effect Of Genetic Polymorphisms Of Drug-metabolizing Enzysupporting

confidence: 65%

“…A gene-dose effect was observed for the number of defective CYP2C19 allele(s), which lends further credence to the involvement of CYP2C19 in zonisamide metabolism in patients [12,38]. Enzyme-inducing AEDs such as carbamazepine, phenytoin and phenobarbital were also incorporated into the population pharmacokinetic models (Table 2).…”

Section: Population Pharmacokinetics Of Aedsmentioning

confidence: 85%

“…The zonisamide clearance in CYP2C19 hetero EMs and PMs was 16% and 30% lower than in homo EMs, respectively. A gene-dose effect was observed for the number of defective CYP2C19 allele(s), which lends further credence to the involvement of CYP2C19 in the metabolism of zonisamide in patients [12,129]. Conversely, the CYP3A5*3 genotype did not affect the clearance of zonisamide, indicating that the CYP3A5*3 genotypes do not contribute significantly to the zonisamide pharmacokinetics in Japanese patients with epilepsy [12,129].…”

Section: Effect Of Genetic Polymorphisms Of Drug-metabolizing Enzymentioning

confidence: 96%

“…For example, the phenobarbital clearance in CYP2C9 hetero EMs was 48% lower than in homo EMs (Table 2) [12,36]. Valproic acid, a known inhibitor of phenobarbital metabolism, and phenytoin, a substrate of CYP2C9 and CYP2C19, were also incorporated into the PPK models (Table 2).…”

Section: Population Pharmacokinetics Of Aedsmentioning

confidence: 99%

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Update on the Genetic Polymorphisms of Drug-Metabolizing Enzymes in Antiepileptic Drug Therapy

Saruwatari

Ishitsu²,

Nakagawa

2010

Pharmaceuticals

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Genetic polymorphisms in the genes that encode drug-metabolizing enzymes are implicated in the inter-individual variability in the pharmacokinetics and pharmaco-dynamics of antiepileptic drugs (AEDs). However, the clinical impact of these polymorphisms on AED therapy still remains controversial. The defective alleles of cytochrome P450 (CYP) 2C9 and/or CYP2C19 could affect not only the pharmacokinetics, but also the pharmacodynamics of phenytoin therapy. CYP2C19 deficient genotypes were associated with the higher serum concentration of an active metabolite of clobazam, N-desmethylclobazam, and with the higher clinical efficacy of clobazam therapy than the other CYP2C19 genotypes. The defective alleles of CYP2C9 and/or CYP2C19 were also found to have clinically significant effects on the inter-individual variabilities in the population pharmacokinetics of phenobarbital, valproic acid and zonisamide. EPHX1 polymorphisms may be associated with the pharmacokinetics of carbamazepine and the risk of phenytoin-induced congenital malformations. Similarly, the UDP-glucuronosyltransferase 2B7 genotype may affect the pharmacokinetics of lamotrigine. Gluthatione S-transferase null genotypes are implicated in an increased risk of hepatotoxicity caused by carbamazepine and valproic acid. This article summarizes the state of research on the effects of mutations of drug-metabolizing enzymes on the pharmacokinetics and pharmacodynamics of AED therapies. Future directions for the dose-adjustment of AED are discussed.

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Section: Effect Of Genetic Polymorphisms Of Drug-metabolizing Enzysupporting

confidence: 65%

Section: Population Pharmacokinetics Of Aedsmentioning

confidence: 85%

Section: Effect Of Genetic Polymorphisms Of Drug-metabolizing Enzymentioning

confidence: 96%

Section: Population Pharmacokinetics Of Aedsmentioning

confidence: 99%

See 2 more Smart Citations

Update on the Genetic Polymorphisms of Drug-Metabolizing Enzymes in Antiepileptic Drug Therapy

Saruwatari

Ishitsu²,

Nakagawa

2010

Pharmaceuticals

Self Cite

View full text Add to dashboard Cite

show abstract

“…Author concluded that CYP2C9 genotype may affects the PB metabolism in routine care, however further evidence should be verified in other ethnic populations [6]. -Influence of CYP2C19 and CYP3A5 on clearance of zonisamide was assessed in patients with epilepsy with evidence of gene-dose effect for defective CYP2C19 but not for CYP3A5*3 genotype [7]. Further studies are needed to assess the extent of polymorphism in other ethnic populations.…”

Section: Cytochromes P450 and Udp-glucuronosyltransferase Polymorphismentioning

confidence: 99%

Pharmacotherapy in pediatric epilepsy: rational drug and dose selection

Verrotti

Piccorossi

Lasorella

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

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Management of genetic epilepsies: From empirical treatment to precision medicine

Striano

Vari

Mazzocchetti

et al. 2016

Pharmacological Research

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The clinical impact of cytochrome P450 polymorphisms on anti-epileptic drug therapy

Cited by 8 publications

References 62 publications

Update on the Genetic Polymorphisms of Drug-Metabolizing Enzymes in Antiepileptic Drug Therapy

Update on the Genetic Polymorphisms of Drug-Metabolizing Enzymes in Antiepileptic Drug Therapy

Pharmacotherapy in pediatric epilepsy: rational drug and dose selection

Management of genetic epilepsies: From empirical treatment to precision medicine

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