Characterization of covalent binding of tyrosine kinase inhibitors to plasma proteins.

abstract：:The participation of cytochrome P-450 (CYP) isoforms in the metabolism of selegiline was investigated. Experiments using recombinant CYP isoforms expressed in human lymphoblastoid cells showed CYP2B6 to be the major CYP isoform involved with the metabolism of selegiline. CYP1A2 and CYP3A4 also contributed to the metab...

journal_title：Drug metabolism and pharmacokinetics

authors： Kamada T,Chow T,Hiroi T,Imaoka S,Morimoto K,Ohde H,Funae Y

更新日期：2002-01-01 00:00:00

abstract：:Most of cytochrome P450 (CYP) expressions are regulated by nuclear receptors. The regulation pathways of transcription are activated by binding of the ligand to the receptor. Many combination of CYPs and nuclear receptors in transcriptional regulation have been reported. However, we have reported that the combination ...

journal_title：Drug metabolism and pharmacokinetics

authors： Terashima J,Jimma Y,Jimma K,Hakata S,Yachi M,Habano W,Ozawa S

更新日期：2018-08-01 00:00:00

abstract：:The concentration and distribution of a drug or its metabolites in tissues are key factors for understanding drug efficacy or toxicity. Conventional pharmacokinetic studies show that the plasma concentration of a drug is often unrelated to the intra-tissue concentration. Moreover, it is difficult to predict the distri...

journal_title：Drug metabolism and pharmacokinetics

authors： Nishidate M,Hayashi M,Aikawa H,Tanaka K,Nakada N,Miura SI,Ryu S,Higashi T,Ikarashi Y,Fujiwara Y,Hamada A

更新日期：2019-08-01 00:00:00

abstract：:The present study aims is to investigate the metabolic mechanism of Xue-Fu-Zhu-Yu decoction (XFZYD) in the treatment of blood-stasis syndrome in Coronary Heart Disease (CHD). To that end, 30 CHD patients with Blood-Stasis Syndrome (BSS) and 20 healthy subjects were enrolled. LC-Q-TOF/MS analysis determined that in com...

journal_title：Drug metabolism and pharmacokinetics

authors： Yi M,Li Q,Zhao Y,Nie S,Wu N,Wang D

更新日期：2019-10-01 00:00:00

abstract：:This study aimed to develop a drug metabolism prediction platform using knowledge-based prediction models. Site of Metabolism (SOM) prediction models for four cytochrome P450 (CYP) subtypes were developed along with uridine 5'-diphosphoglucuronosyltransferase (UGT) and sulfotransferase (SULT) substrate classification ...

journal_title：Drug metabolism and pharmacokinetics

authors： Hwang S,Shin HK,Shin SE,Seo M,Jeon HN,Yim DE,Kim DH,No KT

更新日期：2020-08-01 00:00:00

abstract：:Nuclear receptors constitutive active/androstane receptor (CAR) and pregnane X receptor (PXR) were originally characterized as transcription factors regulating the hepatic genes that encode drug metabolizing enzymes. Recent works have now revealed that these nuclear receptors also play the critical roles in modulating...

journal_title：Drug metabolism and pharmacokinetics

authors： Konno Y,Negishi M,Kodama S

更新日期：2008-01-01 00:00:00

abstract：:After intravenous bolus administration of aprindine (AP) to conscious guinea pigs, the semilogarithmic plasma concentration versus time curve was linear at a dose of 2 mg/kg, but convex at doses of 5 and 10 mg/kg. AP concentrations immediately after administration (C(p0)) were almost identical, irrespective of the dos...

journal_title：Drug metabolism and pharmacokinetics

authors： Shimizu M,Ohota T,Kishida M,Ogata H

更新日期：2002-01-01 00:00:00

abstract：:Methotrexate (MTX), a drug used for the treatment of certain cancers as well as rheumatoid arthritis, sometimes induces serious interstitial lung injury. Although lung toxicity of MTX is related to its accumulation, the information concerning MTX transport in the lungs is lacking. In this study, we investigated the me...

journal_title：Drug metabolism and pharmacokinetics

authors： Kawami M,Miyamoto M,Yumoto R,Takano M

更新日期：2015-08-01 00:00:00

abstract：:Guanfacine hydrochloride extended-release tablet (GXR) is approved for child and adolescent patients with attention-deficit/hyperactivity disorder (ADHD). The aims of this study were to develop a population pharmacokinetic model of guanfacine after administration of GXR and to evaluate factors influencing the pharmaco...

journal_title：Drug metabolism and pharmacokinetics

authors： Tsuda Y,Matsuo Y,Matsumoto S,Wajima T

更新日期：2019-12-01 00:00:00

abstract：:  Human cytochrome P450 CYP2A6 and CYP2A13 catalyze nicotine metabolisms and mediate activation of tobacco-specific carcinogens including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). In this study, we found rhinacanthins A, B, and C isolated from Rhinac...

journal_title：Drug metabolism and pharmacokinetics

authors： Pouyfung P,Prasopthum A,Sarapusit S,Srisook E,Rongnoparut P

更新日期：2014-01-01 00:00:00

abstract：:Thirty-nine genetic variations, including thirty novel ones, were found in the human SLC29A1 gene, which encodes equilibrative nucleoside transporter 1, from 256 Japanese cancer patients administered gemcitabine. The found novel variations included -8,166G>A, -81,10A>G, -7,947G>A, -7,789T>C, -5,595G>A, -3,803_-3,783de...

journal_title：Drug metabolism and pharmacokinetics

authors： Kim SR,Saito Y,Maekawa K,Sugiyama E,Kaniwa N,Ueno H,Okusaka T,Morizane C,Yamamoto N,Ikeda M,Yoshida T,Minami H,Furuse J,Ishii H,Saijo N,Kamatani N,Ozawa S,Sawada J

更新日期：2006-06-01 00:00:00

abstract：:A population pharmacokinetic substudy design of a new chemical entity was evaluated based on the bias in parameter estimates and the power of detecting a specific subpopulation showing different clearance using a clinical trial simulation approach. The effect of analysis algorithms on type I error was also assessed. T...

journal_title：Drug metabolism and pharmacokinetics

authors： Nakade S,Nishibori A,Okamoto H,Higuchi S

更新日期：2004-10-01 00:00:00

abstract：:The objectives of this study were to evaluate the relative contribution of the direct pathway in overall brain transport for 17 model drugs with different physicochemical properties after nasal administrations and to identify factors that govern the fraction of the dose transported to the brain via the direct pathway ...

journal_title：Drug metabolism and pharmacokinetics

authors： Lee KR,Maeng HJ,Chae JB,Chong S,Kim DD,Shim CK,Chung SJ

更新日期：2010-01-01 00:00:00

abstract：:Nevirapine (NVP) is widely used as a non-nucleoside reverse transcriptase inhibitor of HIV-1, however, it is associated with severe skin and liver injury. The mechanisms of these adverse reactions are not yet clear, but the metabolic activation of NVP is thought to be related to the injury process. Until now, several ...

journal_title：Drug metabolism and pharmacokinetics

authors： Tateishi Y,Ohe T,Yasuda D,Takahashi K,Nakamura S,Kazuki Y,Mashino T

更新日期：2020-04-01 00:00:00

abstract：:This study aimed to evaluate the relationship between the concentrations of plasma fentanyl and serum 4β-hydroxycholesterol based on CYP3A5 genotype and gender in cancer patients. Thirty-three Japanese cancer patients treated with transdermal fentanyl were enrolled. The concentrations of plasma fentanyl and norfentany...

journal_title：Drug metabolism and pharmacokinetics

authors： Ishida T,Naito T,Sato H,Kawakami J

更新日期：2016-06-01 00:00:00

abstract：:Five novel single nucleotide polymorphisms (SNPs) were found in the EPHX1 gene from 96 Japanese epileptic patients. The detected SNPs were as follows: 1) SNP, MPJ6_EX1009; GENE NAME, EPHX1 ACCESSION NUMBER, NT_004525.12; LENGTH, 25 bases; 5'-CCTCACTTCAGTG/ACTGGGCTTTGCC-3'. 2) SNP, MPJ6_EX1013; GENE NAME, EPHX1; ACCESS...

journal_title：Drug metabolism and pharmacokinetics

authors： Shiseki K,Itoda M,Saito Y,Nakajima Y,Maekawa K,Kimura H,Goto Y,Saitoh O,Katoh M,Ohnuma T,Kawai M,Sugai K,Ohtsuki T,Suzuki C,Minami N,Ozawa S,Sawada J

更新日期：2003-01-01 00:00:00

abstract：:Oligopeptide transporter PEPT1 is thought to be involved in the intestinal absorption and renal reabsorption of peptides and therapeutic agents. The driving force of PEPT1 is H+ gradient, a part of which is supplied by Na+/H+ exchanger (NHE) expressed on the apical surface of the epithelium although molecular identifi...

journal_title：Drug metabolism and pharmacokinetics

authors： Watanabe C,Kato Y,Ito S,Kubo Y,Sai Y,Tsuji A

更新日期：2005-12-01 00:00:00

abstract：:In this study, a simple in vitro method for detecting human P450 (CYP) quasi-irreversible and irreversible inhibitors was evaluated. For the method, cDNA-expressed CYPs were applied to microtiter plate assays, CYP inhibitors were co-incubated with fluorometric substrates, and IC(50) were continuously measured (without...

journal_title：Drug metabolism and pharmacokinetics

authors： Naritomi Y,Teramura Y,Terashita S,Kagayama A

更新日期：2004-02-01 00:00:00

abstract：:Accumulating evidences have shown that diabetes is often accompanied with depression, thus it is possible that oral antidiabetic agent glyburide and antidepressive agent paroxetine are co-administered in diabetic patients. The aim of this study was to assess interactions between glyburide and paroxetine in rats. Effec...

journal_title：Drug metabolism and pharmacokinetics

authors： Jiang S,Zhao W,Chen Y,Zhong Z,Zhang M,Li F,Xu P,Zhao K,Li Y,Liu L,Liu X

更新日期：2015-06-01 00:00:00

abstract：:Cytochrome P450 (P450) constitutes a superfamily of enzymes which activate dioxygen and carry out monooxygenation reactions of large numbers of endogenous and xenobiotic compounds. Drug metabolism is a particularly important P450 function, and, therefore, elucidating the metabolic products and pathways of drugs is ess...

journal_title：Drug metabolism and pharmacokinetics

authors： Yasui H,Hayashi S,Sakurai H

更新日期：2005-02-01 00:00:00

abstract：:Aldehyde oxidase contributes to drug metabolism and pharmacokinetics (PK), and a few clinical studies were discontinued because of aldehyde oxidase metabolism. Its AOX1, AOX3, AOX3L1, and AOX4 isoforms are expressed in mammals, and species differences in expression profiles reflect differences in drug metabolism and P...

journal_title：Drug metabolism and pharmacokinetics

authors： Sanoh S,Tayama Y,Sugihara K,Kitamura S,Ohta S

更新日期：2015-02-01 00:00:00

abstract：:Studies of the genetic regulation involved in drug metabolizing enzymes and drug transporters are of great interest to understand the molecular mechanisms of drug response and toxic events. Recent reports have revealed that hydrophobic ligands and several nuclear receptors are involved in the induction or down-regulat...

journal_title：Drug metabolism and pharmacokinetics

authors： Nakata K,Tanaka Y,Nakano T,Adachi T,Tanaka H,Kaminuma T,Ishikawa T

更新日期：2006-12-01 00:00:00

abstract：:Specific antibody production is an important issue in crossover pharmacokinetic (PK) studies of protein-based formulations. We recently reported that intravenous co-administration of tacrolimus with multiple human interferon-alpha (h-IFN) administrations successfully suppressed the production of anti-h-IFN antibodies ...

journal_title：Drug metabolism and pharmacokinetics

authors： Yamazaki H,Miyake M,Kamada N,Nishibayashi T,Mukai T,Odomi M,Ishida T,Kiwada H

更新日期：2010-01-01 00:00:00

abstract：:A population pharmacokinetic (PK) model for meropenem in Japanese pediatric patients with various infectious diseases was developed based on 116 plasma concentrations from 50 pediatric patients. The population PK parameters developed in this analysis are useful for calculation of the percent time above minimum inhibit...

journal_title：Drug metabolism and pharmacokinetics

authors： Ohata Y,Tomita Y,Nakayama M,Kozuki T,Sunakawa K,Tanigawara Y

更新日期：2011-01-01 00:00:00

abstract：:Standard incubation procedures for carrying out microsomal assays involve the use of less than 1% w/v organic solvents to minimize the potential inhibitory effects of organic solvents on metabolic activity. This presents a practical limitation for poorly soluble xenobiotics, which cannot be incubated at concentrations...

journal_title：Drug metabolism and pharmacokinetics

authors： Argikar UA,Liang G,Bushee JL,Hosagrahara VP,Lee W

更新日期：2011-01-01 00:00:00

abstract：:In a clinical setting, changes in pharmacokinetics due to drug-drug interactions can often directly affect the therapeutic safety and efficacy of drugs. Recently, interest has been shown in drug-drug interactions in the intestine. It is now recognized that changes in the functions of drug transporters substantially in...

journal_title：Drug metabolism and pharmacokinetics

authors： Segawa M,Ogura J,Seki S,Itagaki S,Takahashi N,Kobayashi M,Hirano T,Yamaguchi H,Iseki K

更新日期：2013-01-01 00:00:00

abstract：:Nifedipine is one of drugs that have been suggested to undergo significant first-pass metabolism by cytochrome P450 (CYP) 3A in the intestine, based mainly on pharmacokinetic analyses of in vivo observations. To further substantiate this suggestion, we examined the metabolic extraction of nifedipine from the rat small...

journal_title：Drug metabolism and pharmacokinetics

authors： Iwao T,Inoue K,Hayashi Y,Yuasa H,Watanabe J

更新日期：2002-01-01 00:00:00

abstract：:The bile salt export pump (BSEP) encoded by ABCB11 is located in the canalicular membrane of hepatocytes and mediates the secretion of numerous conjugated bile salts into the bile canaliculus. In this study, 28 ABCB11 exons (including non-coding exon 1) and their flanking introns were comprehensively screened for gene...

journal_title：Drug metabolism and pharmacokinetics

authors： Kim SR,Saito Y,Itoda M,Maekawa K,Kawamoto M,Kamatani N,Ozawa S,Sawada J

更新日期：2009-01-01 00:00:00

abstract：:We discovered a novel single nucleotide polymorphism (SNP) at position 325 (G325A) in exon 5 of the multidrug-resistance 1 (MDR1) gene in a study of 37 healthy Japanese subjects. Details are as follows. SNP, 020614Honda001; GENE NAME, human P-glycoprotein (MDR1); ACCESSION NUMBER, M29427; LENGTH, 25 bases; 5'-ATGAATCT...

journal_title：Drug metabolism and pharmacokinetics

authors： Honda T,Dan Y,Koyabu N,Ieiri I,Otsubo K,Higuchi S,Ohtani H,Sawada Y

更新日期：2002-01-01 00:00:00

abstract：:Medication therapy is the first line of treatment in the management of epilepsy. Fetal exposure to valproic acid (VPA), an antiepileptic drug, poses an elevated risk of teratogenicity in early pregnancy. Some studies have reported that monocarboxylate transporters (MCTs) may be involved in the placental transport of V...

journal_title：Drug metabolism and pharmacokinetics

authors： Ishiguro Y,Furugen A,Narumi K,Nishimura A,Hirano T,Kobayashi M,Iseki K

更新日期：2018-12-01 00:00:00