A summary of the current drug interaction guidance from the European Medicines Agency and considerations of future updates.

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：: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：UNLABELLED:Better prediction of drug disposition prior to the clinical trial is critical for the efficient development of new drugs. The purpose of this study is to develop a novel multiple assessment methodology of hepatocellular drug disposition from drug uptake to efflux including biliary and basolateral excretion, ...

journal_title：Drug metabolism and pharmacokinetics

authors： Takahashi R,Ichikawa H,Kanda K

更新日期：2016-04-01 00:00:00

abstract：:Polymorphic human flavin-containing monooxygenase (FMO) 3 is an important drug-metabolizing enzyme for nitrogen- or sulfur-containing compounds. Cynomolgus macaques, a non-human primate species widely used in drug metabolism studies, have corresponding FMO3 molecular and enzymatic similarities to humans; however, gene...

journal_title：Drug metabolism and pharmacokinetics

authors： Uno Y,Shimizu M,Yoda H,Origuchi Y,Yamazaki H

更新日期：2019-02-01 00:00:00

abstract：:We performed a caffeine (N-3-methyl-13C) breath test (CafeBT) to determine whether it can be employed to identify caffeine metabolism-associated single nucleotide polymorphisms. The study included 130 healthy adults (mean age: 21.9 years). Saliva was collected using an Oragene®•DNA saliva collection kit. Breath sample...

journal_title：Drug metabolism and pharmacokinetics

authors： Ishii M,Ishii Y,Nakayama T,Takahashi Y,Asai S

更新日期：2020-06-01 00:00:00

abstract：:The mRNA levels of human cytochrome P450 (CYP)2Cs and CYP3As in primary cultures of freshly isolated human hepatocytes were assessed after exposure to NO-1886 and rifampicin, a typical inducer of CYP3As. mRNA levels were analyzed by real-time RT-PCR using an ABI PRISM 7700 Sequence Detector system. Exposure to NO-1886...

journal_title：Drug metabolism and pharmacokinetics

authors： Morioka Y,Nishimura M,Imai T,Suzuki S,Harada M,Satoh T,Naito S

更新日期：2006-02-01 00:00:00

abstract：:The hepatic uptake transporter organic anion transporting polypeptide (OATP) 1B1 is inhibited by some uremic toxins; however, direct inhibition can only partially explain the delayed systemic elimination of substrate drugs in renal failure patients. This study aimed to examine the long-lasting inhibition of OATP1B1 by...

journal_title：Drug metabolism and pharmacokinetics

authors： Masuo Y,Fujita KI,Mishiro K,Seba N,Kogi T,Okumura H,Matsumoto N,Kunishima M,Kato Y

更新日期：2020-12-01 00:00:00

abstract：:Pairs of forward and reverse primers and TaqMan probes specific to each human nuclear receptor were prepared. Analysis of the mRNA expression level of each target of 43 nuclear receptors in total RNA from single and pooled specimens of various human organs (liver, kidney, adrenal gland, lung, heart, brain, cerebellum,...

journal_title：Drug metabolism and pharmacokinetics

authors： Nishimura M,Naito S,Yokoi T

更新日期：2004-04-01 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：:Twenty genetic variations, including seven novel ones, were found in the human SLC22A1 gene, which encodes organic cation transporter 1, from 116 Japanese individuals. The novel variations were as follows: -94C>A in the 5'-untranslated region (A of the translation start codon is numbered +1 in the cDNA sequence; MPJ6_...

journal_title：Drug metabolism and pharmacokinetics

authors： Itoda M,Saito Y,Maekawa K,Hichiya H,Komamura K,Kamakura S,Kitakaze M,Tomoike H,Ueno K,Ozawa S,Sawada J

更新日期：2004-08-01 00:00:00

abstract：:In the present study, we identified three novel single nucleotide polymorphisms (SNPs), 147C>T in exon 2 (silent), 602G>C in exon 3 (Arg201Pro), and 1134C>T in exon 4 (silent), in the gene of bile acid CoA: amino acid N-acyltransferase (BAAT) by resequencing the entire coding region and the exon-intron junctions of 10...

journal_title：Drug metabolism and pharmacokinetics

authors： Tougou K,Fukuda T,Ito T,Yamazaki H,Fujio Y,Azuma J

更新日期：2007-04-01 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：: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：:Clinical studies have revealed that some fluoroquinolones may cause severe adverse effects when co-administered with substrates of CYP1A2. Our previous study showed antofloxacin (ATFX) was responsible for mechanism-based inhibition (MBI) of the metabolism of phenacetin in rats. In the clinical setting, ATFX is likely ...

journal_title：Drug metabolism and pharmacokinetics

authors： Pan X,Wang P,Hu N,Liu L,Liu X,Xie L,Wang G

更新日期：2011-01-01 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：: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：:To investigate the transport function of the blood-brain barrier (BBB), we employed an in vitro model of the BBB, consisting of a co-culture of porcine brain capillary endothelial cells (BCECs) with rat astrocytes. Porcine BCECs were cultured on a filter insert with rat astrocytes on the underlying plastic well. Rat a...

journal_title：Drug metabolism and pharmacokinetics

authors： Kido Y,Tamai I,Nakanishi T,Kagami T,Hirosawa I,Sai Y,Tsuji A

更新日期：2002-01-01 00:00:00

abstract：:A novel method for the prediction of drug-drug interaction has been established based on the in vitro metabolic stability in the "serum incubation method" using cryopreserved human hepatocytes suspended in 100% human serum. As a novel approach, the inhibitory effect of inhibitors on the metabolism of substrates during...

journal_title：Drug metabolism and pharmacokinetics

authors： Shibata Y,Takahashi H,Chiba M,Ishii Y

更新日期：2008-01-01 00:00:00

abstract：:DDI could be caused by the inhibition of OATP-mediated hepatic uptakes. The aim of this study is to set the risk criteria for the compounds that would cause DDI via OATP inhibition at the drug discovery stage. The IC50 values of OATP inhibitors for human OATP-mediated atorvastatin uptake were evaluated in the expressi...

journal_title：Drug metabolism and pharmacokinetics

authors： Nakakariya M,Goto A,Amano N

更新日期：2016-10-01 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：: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：:The ATP-binding cassette transporter, ABCG2, which is expressed at high levels in the intestine and liver, functions as an efflux transporter for many drugs, including clinically used anticancer agents such as topotecan and the active metabolite of irinotecan (SN-38). In this study, to elucidate the linkage disequilib...

journal_title：Drug metabolism and pharmacokinetics

authors： Maekawa K,Itoda M,Sai K,Saito Y,Kaniwa N,Shirao K,Hamaguchi T,Kunitoh H,Yamamoto N,Tamura T,Minami H,Kubota K,Ohtsu A,Yoshida T,Saijo N,Kamatani N,Ozawa S,Sawada J

更新日期：2006-04-01 00:00:00

abstract：:Tralokinumab is a human monoclonal antibody in clinical development for asthma and atopic dermatitis that specifically neutralizes interleukin-13. This phase I, single-blind, randomized, placebo-controlled, single ascending-dose study assessed the safety, tolerability, pharmacokinetics (PK), and immunogenicity of subc...

journal_title：Drug metabolism and pharmacokinetics

authors： Baverel P,She D,Piper E,Ueda S,Yoshioka T,Faggioni R,Gevorkyan H

更新日期：2018-06-01 00:00:00

abstract：:Pitavastatin undergoes little hepatic metabolism but it is a substrate for uptake and efflux transporters, particularly OATP1B1 (gene SLCO1B1). A previous study in 8 Japanese healthy subjects showed that co-administration with grapefruit juice (GFJ) resulted in a small increase in systemic exposure to pitavastatin. We...

journal_title：Drug metabolism and pharmacokinetics

authors： Hu M,Mak VW,Yin OQ,Chu TT,Tomlinson B

更新日期：2013-01-01 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：: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：:Maleic acid (MA) was purposefully adulterated in an array of starch-based foods in Taiwan, inciting a food safety incident. Due to limited data on the pharmacokinetics and bioavailability of ingested MA, we studied pharmacokinetic (PK) parameters in serum and urine of Sprague Dawley rats. Three groups of male and fema...

journal_title：Drug metabolism and pharmacokinetics

authors： Wu C,Chen HC,Luo YS,Chiang SY,Wu KY

更新日期：2016-12-01 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：: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