Significance of aldehyde oxidase during drug development: Effects on drug metabolism, pharmacokinetics, toxicity, and efficacy.

abstract：:The roots of Sophora flavescens (Sf) have been widely used as a herbal medicine for the treatment of diarrhea, gastrointestinal hemorrhage, and eczema. Cytochrome P450 (P450) forms including CYP1A2, CYP2B, CYP2E1, and CYP3A participate in the oxidative metabolism of theophylline, which is an important bronchodilation ...

journal_title：Drug metabolism and pharmacokinetics

authors： Ueng YF,Tsai CC,Lo WS,Yun CH

更新日期：2010-01-01 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：:The aim of this study was to investigate the impact of genetic polymorphisms in the metabolic and cellular transport pathway of methotrexate (MTX) on the clinical outcome of MTX monotherapy in Japanese rheumatoid arthritis (RA) patients. Fifty-five patients were treated with MTX monotherapy at a dose of 4-10 mg/week. ...

journal_title：Drug metabolism and pharmacokinetics

authors： Kato T,Hamada A,Mori S,Saito H

更新日期：2012-01-01 00:00:00

abstract：:Drug metabolizing activities of cytochromes P450 (P450s, or CYPs) 3A4 and 3A5 in liver microsomes from the cynomolgus monkey [Macaca fascicularis (mf)] were investigated and compared with those of human P450 3A enzymes. Low activities for dealkylation of ethoxyresorufin and pentoxyresorufin were seen in recombinant mo...

journal_title：Drug metabolism and pharmacokinetics

authors： Iwasaki K,Murayama N,Koizumi R,Uno Y,Yamazaki H

更新日期：2010-01-01 00:00:00

abstract：:We have recently found that the frequency of OATP-C*15 is significantly higher in patients who experienced myopathy after receiving pravastatin or atorvastatin than in patients without myopathy. However, there were two patients who experienced pravastatin-induced myopathy despite the fact that they did not possess OAT...

journal_title：Drug metabolism and pharmacokinetics

authors： Morimoto K,Oishi T,Ueda S,Ueda M,Hosokawa M,Chiba K

更新日期：2004-12-01 00:00:00

abstract：:Protein kinases are potential drug targets for the treatment of a variety of diseases, including cancer. In particular, specific tyrosine kinase inhibitors are rapidly being developed as new drugs for the inhibition of malignant cell growth and metastasis formation. Most of these newly developed tyrosine kinase inhibi...

journal_title：Drug metabolism and pharmacokinetics

authors： Saito H,An R,Hirano H,Ishikawa T

更新日期：2010-01-01 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：: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 enzyme activities of CYP2D6 and CYP2C19 show a genetic polymorphism, and the frequency of poor metabolizers (PMs) on these enzymes depends on races. We have analyzed frequencies of mutant alleles and PMs based on the published data in previous study (Shimizu, T. et al.: Bioinformatics research on inter-racial diff...

journal_title：Drug metabolism and pharmacokinetics

authors： Shimizu T,Ochiai H,Asell F,Yokono Y,Kikuchi Y,Nitta M,Hama Y,Yamaguchi S,Hashimoto M,Taki K,Nakata K,Aida Y,Ohashi A,Ozawa N

更新日期：2003-01-01 00:00:00

abstract：:New SRM (selected reaction monitoring) data dependent exclusion (MS)(n) measurement makes it possible to obtain MS(3) fragmentation data for all MS(2) fragments, useful for structural determination of drug metabolites using ESI ion trap. MS(2) fragments are produced by cleavage of all protonated molecules at the lone ...

journal_title：Drug metabolism and pharmacokinetics

authors： Tozuka Z,Kaneko H,Shiraga T,Beppu M,Niwa T,Kawamura A,Kagayama A

更新日期：2003-01-01 00:00:00

abstract：:Over the past few decades, monoclonal antibodies (mAbs) have become one of the most important and fastest growing classes of therapeutic molecules, with applications in a wide variety of disease areas. As such, understanding of the determinants of mAb pharmacokinetic (PK) processes (absorption, distribution, metabolis...

journal_title：Drug metabolism and pharmacokinetics

authors： Glassman PM,Balthasar JP

更新日期：2019-02-01 00:00:00

abstract：:Analysis of mRNAs from liver biopsy samples of patients with chronic hepatitis C revealed that the levels of nuclear receptor expression were correlated with those of drug-metabolizing enzymes and transporters in relation to the development of fibrosis. Overall, the median mRNA level was largely dependent on fibrosis ...

journal_title：Drug metabolism and pharmacokinetics

authors： Hanada K,Nakai K,Tanaka H,Suzuki F,Kumada H,Ohno Y,Ozawa S,Ogata H

更新日期：2012-01-01 00:00:00

abstract：:Chemotherapy-induced neutropenia is one of the major adverse events which results in the reduction of chemotherapy. Doxorubicin is a substrate of the adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) transporter; reportedly, ABCB1 polymorphisms influence doxorubicin pharmacokinetics. We evaluated th...

journal_title：Drug metabolism and pharmacokinetics

authors： Ikeda M,Tsuji D,Yamamoto K,Kim YI,Daimon T,Iwabe Y,Hatori M,Makuta R,Hayashi H,Inoue K,Nakamichi H,Shiokawa M,Itoh K

更新日期：2015-04-01 00:00:00

abstract：:Fast disintegrating lansoprazole tablet (LFDT) has been developed as a multiple unit formulation and evaluated using human subjects as compared to the conventional lansoprazole (LPZ) capsule containing enteric coated granules. Twelve healthy male volunteers, who were confirmed as extensive metabolizers (EMs) based on ...

journal_title：Drug metabolism and pharmacokinetics

authors： Iwasaki K,Yoshikawa Y,Shibata N,Takada K,Sakurai Y,Takagi N,Irie S,Nakamura K

更新日期：2004-06-01 00:00:00

abstract：:The object of this analysis was to develop a population pharmacokinetic model of micafungin, a new anti-fungal agent of the echinocandin class, to optimize dosing in Japanese patients with fungal infections. Population pharmacokinetics parameters were determined using NONMEM based on pharmacokinetic data from 198 subj...

journal_title：Drug metabolism and pharmacokinetics

authors： Tabata K,Katashima M,Kawamura A,Kaibara A,Tanigawara Y

更新日期：2006-08-01 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：:Pregnane X receptor (PXR) is a ligand-activated nuclear factor that upregulates the expression of proteins involved in the detoxification and clearance of xenobiotics, primarily cytochrome P450 3A4 (CYP3A4). Structure-activity relationship (SAR) analysis of PXR agonists is useful for avoiding unwanted pharmacokinetics...

journal_title：Drug metabolism and pharmacokinetics

authors： Yoshida S,Yamashita F,Itoh T,Hashida M

更新日期：2012-01-01 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：:The objective of this work was to develop a population pharmacokinetic model to assess the influence of subject covariates on the pharmacokinetics of valsartan in children. Data were collected from a single dose study in 26 hypertensive children ages 1 to 16 years. Subjects received 2 mg/kg valsartan suspension up to ...

journal_title：Drug metabolism and pharmacokinetics

authors： Habtemariam B,Sallas W,Sunkara G,Kern S,Jarugula V,Pillai G

更新日期：2009-01-01 00:00:00

abstract：:Cytochrome P450 2A6 (CYP2A6) is an enzyme involved in the metabolism of tobacco carcinogens, which are important risk factors in lung cancer. We and others have previously reported that CYP2A6*4, a whole-gene deletion polymorphism, is associated with lower risk of lung cancer than the wild-type allele. However, the ge...

journal_title：Drug metabolism and pharmacokinetics

authors： Hosono H,Kumondai M,Arai T,Sugimura H,Sasaki T,Hirasawa N,Hiratsuka M

更新日期：2015-08-01 00:00:00

abstract：:Troglitazone induced an idiosyncratic, hepatocellular injury-type hepatotoxicity in humans. Statistically, double null genotype of glutathione S-transferase isoforms, GSTT1 and GSTM1, was a risk factor, indicating a low activity of the susceptible patients in scavenging chemically reactive metabolites. CYP3A4 and CYP2...

journal_title：Drug metabolism and pharmacokinetics

authors： Ikeda T

更新日期：2011-01-01 00:00:00

abstract：:Microdose (MD) clinical trials have been introduced to obtain human pharmacokinetic data early in drug development. Here we assessed the cost-effectiveness of microdose integrated drug development in a hypothetical model, as there was no such quantitative research that weighed the additional effectiveness against the ...

journal_title：Drug metabolism and pharmacokinetics

authors： Yamane N,Igarashi A,Kusama M,Maeda K,Ikeda T,Sugiyama Y

更新日期：2013-01-01 00:00:00

abstract：:Trimethylaminuria is caused by excessive malodorous trimethylamine excreted via urine and body secretion by decreased hepatic flavin-containing monooxygenase 3 (FMO3) metabolic capacity for transforming non-odorous trimethylamine N-oxide. This study investigates foodstuff first in healthy volunteers for palliative car...

journal_title：Drug metabolism and pharmacokinetics

authors： Shimizu M,Kozono M,Murayama N,Yamazaki H

更新日期：2009-01-01 00:00:00

abstract：:Methyl gallate (MG) and pentagalloyl glucopyranose (PGG) are bioactive phenolic compounds that possess various pharmacological activities. However, the knowledge of hepatic metabolism of MG and PGG is limited. The purpose of this study was to investigate the in vitro glucuronidation of MG and PGG using liver microsome...

journal_title：Drug metabolism and pharmacokinetics

authors： Jiamboonsri P,Pithayanukul P,Bavovada R,Leanpolchareanchai J,Gao S,Hu M

更新日期：2016-08-01 00:00:00

abstract：:It has been reported that inhibition of the P-glycoprotein (P-gp) results in the improved absorption of P-gp substrate in the intestinal tract. In fact, the increased permeability of P-gp substrate across the intestinal epithelium was observed following inhibition of P-gp in in vitro experiments. To develop the formul...

journal_title：Drug metabolism and pharmacokinetics

authors： Iida A,Tomita M,Hayashi M

更新日期：2005-04-01 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：:Tacrolimus is a widely used immunosuppressant after organ transplantation. The narrow therapeutic window and individual variability in tacrolimus pharmacokinetics make management of this agent a great challenge. This study was undertaken to determine the association of clinical markers, cytochrome P450, family 3, subf...

journal_title：Drug metabolism and pharmacokinetics

authors： Chen D,Guo F,Shi J,Zhang C,Wang Z,Fan J,Peng Z

更新日期：2014-01-01 00:00:00

abstract：:To characterize the renal handling of CS-023 (RO4908463), a novel parenteral carbapenem antibiotic, and meropenem in humans, we examined their affinities as substrates to human renal transporters. In vitro studies on the uptake of [14C]CS-023 and [14C]meropenem were conducted using HEK293 cells expressing human organi...

journal_title：Drug metabolism and pharmacokinetics

authors： Shibayama T,Sugiyama D,Kamiyama E,Tokui T,Hirota T,Ikeda T

更新日期：2007-02-25 00:00:00

abstract：:The interaction between cytochrome P450s (CYP, P450) and UDP-glucuronosyltransferases (UGTs) was studied by co-immunoprecipitation. P450 isoform-selective antibody was used as a probe to co-precipitate UGTs with the P450s from solubilized rat liver microsomes. Antibodies toward CYP3A2, CYP2B2, CYP2C11/13 and CYP1A2 co...

journal_title：Drug metabolism and pharmacokinetics

authors： Ishii Y,Iwanaga M,Nishimura Y,Takeda S,Ikushiro S,Nagata K,Yamazoe Y,Mackenzie PI,Yamada H

更新日期：2007-10-01 00:00:00

abstract：:Dihydrofolate reductase gene (DHFR) 19-bp deletion polymorphisms result in varied DHFR enzymatic activity affecting the risk for preterm delivery, spina bifida, and the efficacy of methotrexate (MTX). Ethnic differences in DHFR 19-bp polymorphisms may be responsible for the divergent findings in previous genetic studi...

journal_title：Drug metabolism and pharmacokinetics

authors： Hayashi H,Horino M,Morishita M,Tazoe Y,Tsuboi S,Matsuyama T,Kosuge K,Yamada H,Tsuji D,Inoue K,Itoh K

更新日期：2010-01-01 00:00:00