当前位置： SCI文献检索 > Drug Metabolism and Pharmacokinetics期刊下所有文献 > Appropriate risk criteria for OATP inhibition at the drug discovery stage based on the clinical relevancy between OATP inhibitors and drug-induced adverse effect.

Appropriate risk criteria for OATP inhibition at the drug discovery stage based on the clinical relevancy between OATP inhibitors and drug-induced adverse effect.

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 expression system. In order to set the risk criteria for OATP inhibition, the relationship was clarified between OATP inhibitory effect and severe adverse effects of OATP substrates, rhabdomyolysis, hyperbilirubinemia and jaundice. Rhabdomyolysis would be caused in the atorvastatin AUC more than 9-fold of that at a minimum therapeutic dose. The atorvastatin AUC was 6- to 9-fold increased with the OATP inhibitors of which IC50 values were ≤1 μmol/L. Hyperbilirubinemia and jaundice would be caused with the OATP inhibitors of which IC50 values were ≤6 μmol/L. This investigation showed that the compounds with IC50 of ≤1 μmol/L would have high risk for OATP-mediated DDI that would cause severe side effects. Before the detailed analysis based on the dosage, unbound fraction in blood and effective concentration to evaluate the clinical DDI potency, this criteria enable high throughput screening and optimize lead compounds at the drug discovery stage.

journal_name

Drug Metab Pharmacokinet

journal_title

Drug metabolism and pharmacokinetics

authors

Nakakariya M,Goto A,Amano N

doi

10.1016/j.dmpk.2016.05.003

subject

Has Abstract

pub_date

2016-10-01 00:00:00

pages

333-339

issue

5

eissn

1347-4367

issn

1880-0920

pii

S1347-4367(16)30023-4

journal_volume

31

pub_type

杂志文章

相关文献

Drug Metabolism and Pharmacokinetics文献大全
  • Effect of nuclear receptor downregulation on hepatic expression of cytochrome P450 and transporters in chronic hepatitis C in association with fibrosis development.

    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

    pub_type： 杂志文章

    doi：10.2133/dmpk.dmpk-11-rg-077

    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

  • Quantitative targeted absolute proteomics for 28 human transporters in plasma membrane of Caco-2 cell monolayer cultured for 2, 3, and 4 weeks.

    abstract：:The purpose of the present study was to evaluate and compare the absolute protein expression levels of 28 drug-related transporters in Caco-2 cell monolayers cultured for 2, 3, and 4 weeks. Plasma membrane fractions of Caco-2 cells cultured on Transwell inserts for 2, 3 and 4 weeks were prepared and digested with tryp...

    journal_title：Drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1016/j.dmpk.2014.11.002

    authors： Uchida Y,Ohtsuki S,Kamiie J,Ohmine K,Iwase R,Terasaki T

    更新日期：2015-04-01 00:00:00

  • Lack of a primary physicochemical determinant in the direct transport of drugs to the brain after nasal administration in rats: potential involvement of transporters in the pathway.

    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

    pub_type： 杂志文章

    doi：10.2133/dmpk.dmpk-10-rg-049

    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

  • Drug-induced idiosyncratic hepatotoxicity: prevention strategy developed after the troglitazone case.

    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

    pub_type： 杂志文章,评审

    doi：10.2133/dmpk.dmpk-10-rv-090

    authors： Ikeda T

    更新日期：2011-01-01 00:00:00

  • Gene-gene interactions between DRD3, MRP4 and CYP2B6 polymorphisms and its influence on the pharmacokinetic parameters of efavirenz in HIV infected patients.

    abstract：:Genetic factors have a significant impact on the PK variability of EFV, much higher than other non-genetic factors, such as demography. In this work we have performed a comprehensive PG analysis of genes encoding the major metabolizing enzymes and transporters of EFV, establishing a clear relationship between the PK p...

    journal_title：Drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1016/j.dmpk.2016.06.001

    authors： Sánchez-Martín A,Cabrera Figueroa S,Cruz R,Porras-Hurtado L,Calvo-Boyero F,Rasool M,Tormes Team.,Domínguez-Gil Hurlé A,Carracedo A

    更新日期：2016-10-01 00:00:00

  • Post-transcriptional regulation of OATP2B1 transporter by a microRNA, miR-24.

    abstract：:Human OATP2B1, a member of organic anion transporting polypeptide family, is expressed in several tissues, including small intestine and liver, and contributes to cellular uptake of endogenous compounds and various drugs. Altered expression of OATP2B1 affects pharmacokinetics of substrate drugs; however, limited infor...

    journal_title：Drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1016/j.dmpk.2020.07.007

    authors： Liu W,Nakano M,Nakanishi T,Nakajima M,Tamai I

    更新日期：2020-12-01 00:00:00

  • The regulation mechanism of AhR activated by benzo[a]pyrene for CYP expression are different between 2D and 3D culture of human lung cancer cells.

    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

    pub_type： 杂志文章

    doi：10.1016/j.dmpk.2018.04.002

    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

  • Involvement of moesin in the development of morphine analgesic tolerance through P-glycoprotein at the blood-brain barrier.

    abstract：:Altered expression of P-glycoprotein (P-gp), a drug efflux transporter expressed by brain capillary endothelial cells (BCECs), may contribute to the development of opioid analgesic tolerance, as demonstrated by cumulative evidence from research. However, the detailed mechanism by which chronic morphine treatment incre...

    journal_title：Drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.2133/dmpk.DMPK-14-RG-042

    authors： Kobori T,Fujiwara S,Miyagi K,Harada S,Nakamoto K,Nakagawa T,Takahashi H,Narita M,Tokuyama S

    更新日期：2014-01-01 00:00:00

  • Protein-protein interactions between rat hepatic cytochromes P450 (P450s) and UDP-glucuronosyltransferases (UGTs): evidence for the functionally active UGT in P450-UGT complex.

    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

    pub_type： 杂志文章

    doi：10.2133/dmpk.22.367

    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

  • Decrease in ciprofloxacin absorption by polyvalent metal cations is not fully attributable to chelation or adsorption.

    abstract：:The drug interaction between new quinolone antibiotics (NQs) and polyvalent metal cation products, leading to a significant decrease in the absorption of NQ, is considered to be attributable to the formation of poorly absorbable chelate and physicochemical adsorption of NQs to cation products. To clarify the mechanism...

    journal_title：Drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.2133/dmpk.dmpk-14-rg-001

    authors： Imaoka A,Hattori M,Akiyoshi T,Ohtani H

    更新日期：2014-01-01 00:00:00

  • Effects of grapefruit juice and SLCO1B1 388A>G polymorphism on the pharmacokinetics of pitavastatin.

    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

    pub_type： 杂志文章,随机对照试验

    doi：10.2133/dmpk.dmpk-12-rg-067

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

    更新日期：2013-01-01 00:00:00

  • Population pharmacokinetic analysis of micafungin in Japanese patients with fungal infections.

    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

    pub_type： 临床试验,杂志文章

    doi：10.2133/dmpk.21.324

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

    更新日期：2006-08-01 00:00:00

  • Thirty novel genetic variations in the SLC29A1 gene encoding human equilibrative nucleoside transporter 1 (hENT1).

    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

    pub_type： 杂志文章

    doi：10.2133/dmpk.21.248

    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

  • Changes in CYP1A2 activity in humans after 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) administration using caffeine as a probe drug.

    abstract：:3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is a ring-substituted amphetamine widely used for recreational purposes. MDMA is predominantly O-demethylenated in humans by cytochrome P450 (CYP) 2D6, and is also a potent mechanism-based inhibitor of the enzyme. After assessing the inhibition and recovery of CYP2D6 i...

    journal_title：Drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.2133/dmpk.dmpk-12-rg-032

    authors： Yubero-Lahoz S,Pardo R,Farre M,Mathuna BÓ,Torrens M,Mustata C,Perez-Mañá C,Langohr K,Carbó ML,de la Torre R

    更新日期：2012-01-01 00:00:00

  • Effect of carrageenan-induced acute peripheral inflammation on the pharmacokinetics and hepatic metabolism of midazolam in rats.

    abstract：:The effect of carrageenan-induced acute peripheral inflammation (API) on the pharmacokinetics of the hepatically metabolizing compound midazolam (MDZ) was investigated in rats. Rats were subcutaneously treated with λ-carrageenan in the hind paw to induce API. When MDZ was intravenously administered in male rats, it wa...

    journal_title：Drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.2133/dmpk.dmpk-14-rg-020

    authors： Kajikawa N,Doi M,Kusaba J,Aiba T

    更新日期：2014-01-01 00:00:00

  • Cost-effectiveness analysis of microdose clinical trials in drug development.

    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

    pub_type： 杂志文章

    doi：10.2133/dmpk.dmpk-12-rg-044

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

    更新日期：2013-01-01 00:00:00

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

    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

    pub_type： 杂志文章,评审

    doi：10.1016/j.dmpk.2014.10.009

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

    更新日期：2015-02-01 00:00:00

  • Mutation in an adaptor protein PDZK1 affects transport activity of organic cation transporter OCTNs and oligopeptide transporter PEPT2.

    abstract：:Genetic polymorphisms in xenobiotic transporters have recently been clarified to be associated with change in drug distribution and disposition. To expand on recent identification of direct interaction and functional regulation of several transporters by a PDZ (PSD95, Dlg and ZO1) domain containing protein PDZK1, the ...

    journal_title：Drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.2133/dmpk.21.375

    authors： Sugiura T,Kato Y,Kubo Y,Tsuji A

    更新日期：2006-10-01 00:00:00

  • Identification of primary equilibrative nucleoside transporter 1 mRNA isoforms resulting from alternative promoter usage in human hepatocytes.

    abstract：:Human equilibrative nucleoside transporter 1 (hENT1) transports various nucleoside analogues into cells. Although the single hENT1 promoter region (P1) and the mRNA isoform (a1) have been characterized previously, we have recently identified additional promoter regions P2 and P3 (which primarily generate c1/2/3 mRNAs ...

    journal_title：Drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.2133/dmpk.dmpk-13-rg-135

    authors： Furihata T,Mizuguchi M,Suzuki Y,Matsumoto S,Kobayashi K,Chiba K

    更新日期：2014-01-01 00:00:00

  • Molecular characterization of UDP-glucuronosyltransferases 3A and 8A in cynomolgus macaques.

    abstract：:UDP-glucuronosyltransferases (UGTs) are drug-metabolizing enzymes essential for the metabolism of endogenous substrates and xenobiotics. The cynomolgus macaque is a nonhuman primate species widely used in drug metabolism studies. The molecular characteristics of UGTs have been extensively investigated in humans, but t...

    journal_title：Drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1016/j.dmpk.2020.05.001

    authors： Uno Y,Yamazaki H

    更新日期：2020-08-01 00:00:00

  • Relationship between ABCB1 gene polymorphisms and severe neutropenia in patients with breast cancer treated with doxorubicin/cyclophosphamide chemotherapy.

    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

    pub_type： 杂志文章

    doi：10.1016/j.dmpk.2014.09.009

    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

  • Applications of MALDI mass spectrometry imaging for pharmacokinetic studies during drug development.

    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

    pub_type： 杂志文章,评审

    doi：10.1016/j.dmpk.2019.04.006

    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

  • Role of biotransformation in drug-induced toxicity: influence of intra- and inter-species differences in drug metabolism.

    abstract：:It is now widely appreciated that drug metabolites, in addition to the parent drugs themselves, can mediate the serious adverse effects exhibited by some new therapeutic agents, and as a result, there has been heightened interest in the field of drug metabolism from researchers in academia, the pharmaceutical industry...

    journal_title：Drug metabolism and pharmacokinetics

    pub_type： 杂志文章,评审

    doi：10.2133/dmpk.dmpk-10-rv-089

    authors： Baillie TA,Rettie AE

    更新日期：2011-01-01 00:00:00

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

    abstract：:Eight covalent tyrosine kinase inhibitors (TKIs) were investigated to determine the characteristics of their covalent binding to plasma proteins. The data revealed that their covalent binding to plasma proteins is of species difference. In addition to the reports on neratinib and pyrotinib, osimertinib, alflutinib, AS...

    journal_title：Drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1016/j.dmpk.2020.07.002

    authors： Liu X,Feng D,Zheng M,Cui Y,Zhong D

    更新日期：2020-10-01 00:00:00

  • Regional difference in P-glycoprotein function in rat intestine.

    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

    pub_type： 杂志文章

    doi：10.2133/dmpk.20.100

    authors： Iida A,Tomita M,Hayashi M

    更新日期：2005-04-01 00:00:00

  • 13C-caffeine breath test identifies single nucleotide polymorphisms associated with caffeine metabolism.

    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

    pub_type： 杂志文章

    doi：10.1016/j.dmpk.2020.03.003

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

    更新日期：2020-06-01 00:00:00

  • Genetic variations of the ABC transporter gene ABCB11 encoding the human bile salt export pump (BSEP) in a Japanese population.

    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

    pub_type： 杂志文章

    doi：10.2133/dmpk.24.277

    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

  • A novel variant allele of OATP-C (SLCO1B1) found in a Japanese patient with pravastatin-induced myopathy.

    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

    pub_type： 杂志文章

    doi：10.2133/dmpk.19.453

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

    更新日期：2004-12-01 00:00:00

  • Genetic polymorphism of bile acid CoA: amino acid N-acyltransferase in Japanese individuals.

    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

    pub_type： 杂志文章

    doi：10.2133/dmpk.22.125

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

    更新日期：2007-04-01 00:00:00

  • An analysis on distribution and inter-relationships of biomarkers under rivaroxaban in Japanese patients with non-valvular atrial fibrillation (CVI ARO 1).

    abstract：:Prothrombin time (PT) has been widely used for measuring anticoagulation intensity under rivaroxaban therapy, but precise information has not been well established yet. Consecutive 96 non-valvular atrial fibrillation (NVAF) under rivaroxaban between Jan/June, 2015 were recruited. Serum concentration (SC) and PT with 5...

    journal_title：Drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1016/j.dmpk.2018.02.002

    authors： Suzuki S,Yamashita T,Kasai H,Otsuka T,Sagara K

    更新日期：2018-08-01 00:00:00