Combination Analysis in Genetic Polymorphisms of Drug-Metabolizing Enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A5 in the Japanese Population

Ota, Tomoko; Kamada, Yasuhiro; Hayashida, Miyeko; Iwao-Koizumi, Kyoko; Murata, Shigenori; Kinoshita, Kenji

doi:10.7150/ijms.10263

Cited by 51 publications

(42 citation statements)

References 36 publications

(48 reference statements)

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“…Ota et al investigated the prevalence of the most common allelic variants of polymorphic CYP enzymes. They indicated that for CYP1A2, 5%, 37% and 58% of Japanese population were poor, intermediate and extensive metabolizers, respectively . These results are comparable to the CYP1A2 genotype frequencies reported in Caucasians, indicating 10%, 44% and 46% are poor, intermediate and extensive metabolizers, respectively .…”

Section: Discussionmentioning

confidence: 59%

Pharmacokinetics and safety of single and multiple doses of rasagiline in healthy Japanese and caucasian subjects

Elgart

Rabinovich‐Guilatt

Eyal

et al. 2018

Basic Clin Pharma Tox

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As of March 2018, rasagiline is approved for the treatment of Parkinson disease in 55 countries including Japan. The present study evaluated the pharmacokinetics (PK) and safety of rasagiline in healthy Japanese and Caucasian subjects following single and multiple administrations of three rasagiline doses. In this double-blind, placebo-controlled study, 64 healthy subjects (32 Japanese and 32 Caucasian) received either rasagiline (0.5, 1.0, or 2.0 mg) or placebo for 10 days with PK sampling for single-dose administration on day 1 and for multiple administration on day 10. Regardless of administration schedule, rasagiline plasma concentrations and dose-related increases in exposure parameters were similar between Japanese and Caucasians. Rasagiline accumulation (2-fold for 0.5 mg and 3-fold for 1.0 mg and 2.0 mg doses) following multiple administration was similar across the ethnic groups. Geometric mean ratios (GMR) comparing Japanese to Caucasians for AUC , C and AUC following single administration were 1.38, 1.17 and 1.38 for 0.5 mg; 1.22, 1.20 and 1.22 at 1.0 mg; and 1.02, 1.00 and 1.02 at for 2.0 mg. GMR for AUC and C following multiple administration were 1.43 and 1.06 at 0.5 mg, 1.06 and 1.00 at 1.0 mg, and 1.09 and 1.07 at 2.0 mg. Safety measures were unremarkable and similar between Caucasian and Japanese subjects. Comparable systemic exposure and safety parameters were demonstrated for rasagiline administered to healthy Japanese and Caucasian subjects.

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Section: Discussionmentioning

confidence: 59%

Pharmacokinetics and safety of single and multiple doses of rasagiline in healthy Japanese and caucasian subjects

Elgart

Rabinovich‐Guilatt

Eyal

et al. 2018

Basic Clin Pharma Tox

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“…Two hundred and eleven studies not fulfilling the eligibility criteria were further excluded. Finally, a total of 86 studies were included in this review. These included 25, 24, 20 and 17 studies on CYP2C9 , CYP2C19 , CYP2D6 and CYP3A5 , respectively.…”

Section: Resultsmentioning

confidence: 99%

CYP2C9, CYP2C19, CYP2D6 and CYP3A5 polymorphisms in South‐East and East Asian populations: A systematic review

2019

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Summary What is known and objective Genetic polymorphism is one of the most important factors responsible for interindividual and interethnic variability in drug response. Studies in major populations, ie, Caucasians, Asians, and Africans, have provided evidence of differences in the genotype frequencies of major drug‐metabolizing enzyme cytochrome P450 (CYP). This study aimed to review systematically, all relevant articles related to the genetic polymorphisms in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 in South‐East and East Asian (SEEA) populations. Methods Articles that report genetic polymorphisms, genotype frequencies and allele frequencies in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 were retrieved from the PubMed database. Results and discussions A total of 86 studies that fulfilled the eligibility criteria representing different ethnic populations of SEEA, ie, Burmese, Chinese, Japanese, Karen ethnic minority, Korean, Malaysian, Philippino, Singaporean, Taiwanese, Thai, Indonesian, and Vietnamese, were included in the analysis. In general, the genotype frequencies across SEEA populations are comparable. The CYP2C9*1/*1 (69.3%‐99.1%), *1/*3 (2.3%‐20.1%) and *3/*3 (0%‐2.2%) genotypes are reported in most SEEA populations. Six major CYP2C19 genotypes, ie, *1/*1 (6.25%‐88.07%), *1/*2 (21.5%‐86.46%), *1/*3 (0.8%‐15.8%), *2/*2 (3.4%‐14.5%), *2/*3 (0%‐7.3%) and *3/*3 (0%‐10.2%), are reported in most SEEA populations. Major CYP2D6 genotypes include *10/*10 (0%‐69.6%), *1/*1 (0%‐61.21%) and *1/*10 (0%‐62.0%). Major CYP3A5 genotypes are *3/*3 (2.0%‐71.4%), *1/*3 (16.0%‐57.1%) and *1/*1 (0%‐82.0%). Genotyping of abnormal genotypes of CYP2C9 (*1/*3), CYP2C19 (*1/*2, *1/*3), CYP3A5 (*1/*3) and CYP2D6 (*5/*10) associated with IM (Intermediate metabolizer) status, may be clinically beneficial in SEEA populations. Similarly, with CYP2C19 (*2/*2, *2/*3), CYP2D6 (*5/*5 ) linked to PM (Poor metabolizer), CYP2D6 (*10/*10, *1/*5 and to lesser extent *1/*4, *2/*5, *10/*41, *10/*49, *10/*14) and CYP3A5 (*1/*1) associated with EM (extensive metabolizer). What is new and conclusion Sufficient number of studies has provided comparable results in general. This review suggests that comparable genotype frequencies of CYP2C9, CYP2C19, CYP2D6 and CYP3A5 exist among the SEEA populations. It is noted that more research data are reported from East Asians compared with South‐East Asians. Concerned efforts are required to establish partnerships among SEEA countries that will ensure sufficient data from South‐East Asian countries which will assist in establishing the databases for SEEA populations.

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“…Genes encoding proteins involved in drug metabolism have been associated with more than one ADR, including the P450 genes ( CYP34A (58), CYP2C9 (59)), myeloperoxidase (60), and the glutamate-cysteine ligase catalytic subunit gene GCLC (61). For DILI, polymorphic variants of genes involved in the mitochondrial anti-defense pathway, such as Nrf-2 , may play particularly informative roles (62).…”

Section: Susceptibility Genes Shared Between Drug Hypersensitivity Rementioning

confidence: 99%

New approaches for predicting T cell–mediated drug reactions: A role for inducible and potentially preventable autoimmunity

Michels

Ostrov

2015

Journal of Allergy and Clinical Immunology

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Adverse drug reactions (ADRs) are commonplace and occur when a drug binds to its intended pharmacological target (Type A ADR) or an unintended target (Type B ADR). Immunologically mediated Type B ADRs, such as drug hypersensitivity syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN), can be severe and result in a diverse set of clinical manifestations that include fever and rash as well as multiple organ failure (liver, kidney, lungs, and/or heart) in the case of drug hypersensitivity syndrome. There is increasing evidence that specific HLA alleles influence the risk of drug reactions. Several features of T cell–mediated ADRs are strikingly similar to those displayed by autoimmune diseases like type I diabetes, such as strong HLA association, organ-specific adaptive immune responses, viral involvement, and activation of innate immunity. There is a need to better predict patient populations at risk for developing immunologically mediated Type B ADRs. Since methods to predict type 1 diabetes using genetic and immunological biomarkers have been developed to a high level of accuracy (predicting 100% of individuals likely to progress), new research strategies based on these methods may also improve the ability to predict drug hypersensitivity.

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Combination Analysis in Genetic Polymorphisms of Drug-Metabolizing Enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A5 in the Japanese Population

Cited by 51 publications

References 36 publications

Pharmacokinetics and safety of single and multiple doses of rasagiline in healthy Japanese and caucasian subjects

Pharmacokinetics and safety of single and multiple doses of rasagiline in healthy Japanese and caucasian subjects

CYP2C9, CYP2C19, CYP2D6 and CYP3A5 polymorphisms in South‐East and East Asian populations: A systematic review

New approaches for predicting T cell–mediated drug reactions: A role for inducible and potentially preventable autoimmunity

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