A5012223457- Drug Solubulity and Delivery Systems
- Drug-Induced Adverse Reactions
- Drug Transport and Resistance Mechanisms
- Pharmacogenetics and Drug Metabolism
- Cancer therapeutics and mechanisms
- Autoimmune Bullous Skin Diseases
- Colorectal Cancer Treatments and Studies
- Pancreatic and Hepatic Oncology Research
- Analytical Methods in Pharmaceuticals
- Urticaria and Related Conditions
- Pharmacological Effects of Natural Compounds
- Lung Cancer Treatments and Mutations
- Neonatal Health and Biochemistry
- Cancer Genomics and Diagnostics
- Lung Cancer Research Studies
- Helicobacter pylori-related gastroenterology studies
- Metabolism and Genetic Disorders
- Biochemical and Molecular Research
- Pneumocystis jirovecii pneumonia detection and treatment
- Pharmaceutical studies and practices
- Pharmacy and Medical Practices
- Gastrointestinal motility and disorders
- Drug-Induced Hepatotoxicity and Protection
- Pharmacovigilance and Adverse Drug Reactions
- Antibiotics Pharmacokinetics and Efficacy
National Institute of Health Sciences
2008-2020
National Institute of Infectious Diseases
2007-2016
National Institute of Health Sciences
2009-2011
National Cancer Center Hospital East
2006-2009
Kyoto University
2009
National Cancer Centre Japan
2009
PharmacoGenetics (China)
2003-2009
Tokyo Women's Medical University
2006
Hokkaido Institute of Public Health
1998
Osaka University of Pharmaceutical Sciences
1991
Introduction: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening severe cutaneous adverse reactions. Recently, strong associations of HLA-B*1502 HLA-B*5801 with carbamazepine- allopurinol-induced reactions were found in Han Chinese patients, respectively, ethnic differences the have been reported. The objective this study is to clarify involvement Japanese SJS/TEN patients. Methods: HLA-B genotyping was performed on 58 patients between July 2006...
The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe which include reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, toxic epidermal necrolysis. pharmacogenomic basis of phenytoin-related remains unknown.To investigate the genetic factors associated reactions.Case-control study conducted in 2002-2014 among 105 cases (n=61 syndrome/toxic necrolysis n=44 symptoms), 78 exanthema, 130 phenytoin-tolerant...
Objectives SN-38, an active metabolite of irinotecan, is detoxified by glucuronidation with UGT1A isoforms, 1A1, 1A7, 1A9, and 1A10. The pharmacogenetic information on haplotypes covering all these isoforms important for the individualized therapy irinotecan. Associations between pharmacokinetics/pharmacodynamics irinotecan were investigated to identify markers. Methods area under concentration curve ratio (SN-38 glucuronide/SN-38) or toxicities analyzed in 177 Japanese cancer patients...
Summary Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life‐threatening severe cutaneous adverse reactions. Recently, strong associations of HLA‐B*1502 with carbamazepine‐induced SJS/TEN have been found in Han Chinese patients. These confirmed several Asian populations, excluding Japanese. SJS patients carrying HLA‐B*1508, HLA‐B*1511, or HLA‐B*1521, which members the HLA‐B75 type along HLA‐B*1502, were detected studies India Thailand. In current study, we...
Gemcitabine is rapidly metabolized to its inactive metabolite, 2',2'-difluorodeoxyuridine (dFdU), by cytidine deaminase (CDA). We previously reported that a patient with homozygous 208A alleles of CDA showed severe adverse reactions an increase in gemcitabine plasma level. This study extended the investigation effects genetic polymorphisms on pharmacokinetics and toxicities.Genotyping was performed direct sequencing DNA obtained from peripheral blood Japanese gemcitabine-naïve cancer...
Carbamazepine (CBZ) is frequently used for treating epilepsy, but this drug causes cutaneous adverse reactions (cADRs) that may range from mild to severe. It reported recently the human leukocyte antigen HLA-B*1502 associated with Stevens-Johnson syndrome (SJS) induced by CBZ in Han Chinese. We examined HLA class I 15 Japanese patients who fulfilled diagnostic criteria CBZ-induced cADRs (mild 10 and severe = SJS 5). HLA-B*1518, HLA-B*5901 HLA-C*0704 alleles showed higher relative risks...
Ethnic differences in genetic polymorphisms UDP-glucuronosyltransferase 1A1 (<i>UGT1A1</i>) were investigated among African-Americans, Caucasians, and Japanese using samples obtained from 150 individuals for each population. Genotyping of –3279T>G the phenobarbital-responsive enhancer module, TA repeats TATA box, 211G>A (G71R) 686C>A (P229Q) exon 1, three single nucleotide (SNPs) (1813C> T, 1941C>G, 2042C>G) 3′-untranslated region 5 was performed. Eight haplotypes block 1...
We performed comprehensive haplotyping of ABCB1/MDR1 gene blocks using 49 genetic polymorphisms, including seven novel ones, obtained from 145 Japanese subjects. The was divided into four (Blocks -1, 1, 2, and 3) based on linkage disequilibrium analysis polymorphisms. Using an expectation-maximization program, 8, 3 haplotype groups (3, 12, 32, 18 haplotypes) were identified in Blocks 3, respectively. Within Block *1, *2, *4, *6, *8 reported by Kim colleagues (Clin Pharmacol Ther 2001;...
Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are acute inflammatory vesiculobullous reactions of the skin mucous membranes. Cold medicines including non-steroidal anti-inflammatory drugs (NSAIDs) multi-ingredient cold medications reported to be important inciting drugs. We used two sample sets Japanese patients investigate association between HLA genotypes medicine-related SJS/TEN (CM-SJS/TEN), acetaminophen-related (AR-SJS/TEN) with mucosal...
Aim: This preliminary study investigated genomic biomarkers for Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), related to three antiepileptic drugs, zonisamide, phenobarbital phenytoin. Patients & methods:HLA class I HLA-DRB1 loci were genotyped Japanese patients with zonisamide-, phenobarbital- or phenytoin-induced SJS/TEN (n = 12, 8 9, respectively) healthy volunteers 2878). Results: Carrier frequencies of HLA-A*02:07 in zonisamide-induced the general population 41.7...
SN-38 (7-ethyl-10-hydroxycamptothecin), an active metabolite of the antitumor prodrug irinotecan, is conjugated and detoxified to 10-<i>O</i>-β-d-glucuronide by hepatic UDP-glucuronosyltransferase (UGT) 1A1. Recent studies have revealed that other UGT1A isoforms, UGT1A7 UGT1A9, also participate in glucuronidation. Although several genetic polymorphisms are reported for UGT1A1 affect glucuronidation activities, no such been identified UGT1A9. In present study, <i>UGT1A9</i> exon 1 its...
We investigated single-nucleotide polymorphisms of the cytidine deaminase gene (CDA), which encodes an enzyme that metabolizes gemcitabine, to clarify relationship between polymorphism 208G>A and pharmacokinetics toxicity gemcitabine in cancer patients treated with plus cisplatin.Six Japanese cisplatin were examined. Plasma its metabolite 2',2'-difluorodeoxyuridine measured using high-performance liquid chromatography method, CDA genotypes determined DNA sequencing.One patient, a 45-year-old...
CYP2C9 is a polymorphic enzyme that metabolizes number of clinically important drugs. In this study, catalytic activities seven alleles found in Japanese individuals, <i>CYP2C9*3</i> (I359L), <i>*13</i> (L90P), <i>*26</i> (T130R), <i>*28</i> (Q214L), <i>*30</i> (A477T), <i>*33</i> (R132Q), and <i>*34</i> (R335Q), were assessed using three substrates (diclofenac, losartan, glimepiride). When expressed baculovirus-insect cell system, the holo total (apo holo) protein expression levels similar...
To examine whether strict control of clinical trial conditions could reduce apparent differences pharmacokinetic (PK) parameters among ethnic groups.Open-label, single dose PK studies moxifloxacin, simvastatin and meloxicam were conducted in healthy male subjects from three East Asian populations (Japanese, Chinese Koreans) one Caucasian population as a control. These drugs selected because have been reported, even though the backgrounds these are similar. Moxifloxacin (400 mg) was...
Among 242 Japanese pancreatic cancer patients, three patients (1.2%) encountered life-threatening toxicities, including myelosuppression, after gemcitabine-based chemotherapies. Two of them carried homozygous CDA*3 (CDA208G>A [Ala70Thr]), and showed extremely low plasma cytidine deaminase activity gemcitabine clearance. Our results suggest that *3 is a major factor causing gemcitabine-mediated severe adverse reactions among the population.