更新于：2024-11-01

MDR3 x CYP3A4

更新于：2024-11-01

基本信息

关联

项与 MDR3 x CYP3A4 相关的药物

Proliposomal intravesical paclitaxel

靶点

CYP3A4 x MDR3

作用机制

CYP3A4抑制剂 [+1]

在研机构

LIPAC Oncology LLC初创企业 [+1]

原研机构

TesoRx Pharma LLC

在研适应症

膀胱癌 [+3]

非在研适应症

非肌层浸润性膀胱肿瘤 [+1]

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

项与 MDR3 x CYP3A4 相关的临床试验

ChiCTR2300068926 / SuspendedN/AIIT

Acupuncture for the Treatment of Taxane-Induced Peripheral Neuropathy: A single objective performance criteria clinical trial

开始日期2023-03-01

申办/合作机构-

ACTRN12622000081718 / RecruitingN/AIIT

Pilot feasibility randomised sham-controlled trial of electroacupuncture for taxane-induced peripheral neuropathy in Breast Cancer patients during treatment

开始日期2022-06-02

申办/合作机构-

JPRN-jRCTs032210221 / Completed临床2期IIT

Effects and safety of prophylactic compression therapy for taxane-induced peripheral neuropathy

开始日期2021-10-07

申办/合作机构-

100 项与 MDR3 x CYP3A4 相关的临床结果

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100 项与 MDR3 x CYP3A4 相关的转化医学

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0 项与 MDR3 x CYP3A4 相关的专利（医药）

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项与 MDR3 x CYP3A4 相关的文献（医药）

2013-05-01·Hepatology1区 · 医学

Anticholestatic effects of bezafibrate in patients with primary biliary cirrhosis treated with ursodeoxycholic acid

1区 · 医学

Article

作者: Matsuzaki, Yasushi ; Ikegami, Tadashi ; Hirayama, Takeshi ; Imawari, Michio ; Nakamuta, Makoto ; Iwamoto, Junichi ; Miyazaki, Teruo ; Honda, Akira ; Saito, Yoshifumi ; Takikawa, Hajime

Bezafibrate is a widely used hypolipidemic agent and is known as a ligand of the peroxisome proliferator-activated receptors (PPARs). Recently this agent has come to be recognized as a potential anticholestatic medicine for the treatment of primary biliary cirrhosis (PBC) that does not respond sufficiently to ursodeoxycholic acid (UDCA) monotherapy. The aim of this study was to explore the anticholestatic mechanisms of bezafibrate by analyzing serum lipid biomarkers in PBC patients and by cell-based enzymatic and gene expression assays. Nineteen patients with early-stage PBC and an incomplete biochemical response to UDCA (600 mg/day) monotherapy were treated with the same dose of UDCA plus bezafibrate (400 mg/day) for 3 months. In addition to the significant improvement of serum biliary enzymes, immunoglobulin M (IgM), cholesterol, and triglyceride concentrations in patients treated with bezafibrate, reduction of 7α-hydroxy-4-cholesten-3-one (C4), a marker of bile acid synthesis, and increase of 4β-hydroxycholesterol, a marker of CYP3A4/5 activity, were observed. In vitro experiments using human hepatoma cell lines demonstrated that bezafibrate controlled the target genes of PPARα, as well as those of the pregnane X receptor (PXR); down-regulating CYP7A1, CYP27A1, and sinusoidal Na+/taurocholate cotransporting polypeptide (NTCP), and up-regulating CYP3A4, canalicular multidrug resistance protein 3 (MDR3), MDR1, and multidrug resistance-associated protein 2 (MRP2).Conclusion :Bezafibrate is a dual PPARs/PXR agonist with potent anticholestatic efficacy in early-stage PBC patients with an incomplete biochemical response to UDCA monotherapy.

2010-06-01·Journal of Animal Physiology and Animal Nutrition3区 · 农林科学

Dietary flavonoids do not affect vitamin E status in growing rats

3区 · 农林科学

Article

作者: G Rimbach ; H Wiegand ; J Frank ; S Wolffram ; S Wein ; C Boesch-Saadatmandi

SummaryThis study aimed at investigating potential effects of the flavonoids genistein, quercetin and catechin and the role of co‐ingested dietary fat on vitamin E concentrations in rats. In experiment 1, genistein, quercetin and catechin were fed to rats, incorporated into semisynthetic diets at concentrations of 2 g/kg, either as individual compounds or in combination to investigate their individual and possible synergistic actions towards α‐tocopherol in plasma and selected tissues. For experiments 2 and 3, quercetin was selected as a representative model flavonoid to study the effects of the quantity (5% vs. 10%) and type of dietary fat (coconut fat plus corn oil vs. rapeseed oil; experiment 2) and the role of cholesterol (experiment 3) on potential flavonoid‐vitamin E interactions. The concentrations of α‐tocopherol and γ‐tocopherol in the plasma, liver, lung and cortex of flavonoid‐fed rats were not significantly different from the concentrations measured in control rats in all three experiments. However, increasing the amount of coconut fat plus corn oil from 5 to 10% resulted in lower α‐tocopherol concentrations in plasma and tissue. The α‐tocopherol concentrations in the rats fed rapeseed oil were significantly higher than in rats fed coconut fat plus corn oil. The addition of 0.2% cholesterol to the diet did not influence the tocopherol concentrations in plasma and tissue in both quercetin‐supplemented and control rats. Additionally, the mRNA levels of α‐TTP, CYP3A4, CYP4F and Mdr2, which are integral proteins involved in vitamin E homeostasis were measured. Only genistein reduced the Mdr2 mRNA level, but none of the other transcripts. All other flavonoids were without effect. In conclusion, co‐ingested dietary fat appears to influence vitamin E concentrations in rats, but does not seem to be an important determinant of flavonoid‐vitamin E interactions.

2009-02-01·Toxicology and Applied Pharmacology3区 · 医学

Use of mRNA expression to detect the induction of drug metabolising enzymes in rat and human hepatocytes

3区 · 医学

Article

作者: J.-C. Weber ; L. Richert ; D. Pekthong ; N. Blanchard ; S.O. Mueller ; G. Tuschl ; G. Mantion ; C. Abadie

It is important to investigate the induction of cytochrome P450 (CYP) enzymes by drugs. The most relevant end point is enzyme activity; however, this requires many cells and is low throughput. We have compared the CYP1A, CYP2B and CYP3A induction response to eight inducers in rat and human hepatocytes using enzyme activities (CYP1A2 (ethoxyresorufin), 2B (benzoxyresorufin for rat and bupropion for human) and CYP3A (testosterone)) and Taqman Low Density Array (TLDA) analysis. There was a good correlation between the induction of CYP1A2, CYP2B6 and CYP3A4 enzyme activities and mRNA expression in human hepatocytes. In contrast, BROD activities and mRNA expression in rat hepatocytes correlated poorly. However, bupropion hydroxylation correlated well with Cyp2b1 expression in rat hepatocytes. TLDA analysis of a panel of mRNAs encoding for CYPs, phase 2 enzymes, nuclear receptors and transporters revealed that the main genes induced by the 8 compounds tested were the CYPs. AhR ligands also induced UDP-glucuronosyltransferases and glutathione S-transferases in rat and human hepatocytes. The transporters, MDR1, MDR3 and OATPA were the only transporter genes significantly up-regulated in human hepatocytes. In rat hepatocytes Bsep, Mdr2, Mrp2, Mrp3 and Oatp2 were up-regulated. We could then show a good in vivo:in vitro correlation in the induction response of isolated rat hepatocytes and ex-vivo hepatic microsomes for the drug development candidate, EMD392949. In conclusion, application of TLDA methodology to investigate the potential of compounds to induce enzymes in rat and human hepatocytes increases the throughput and information gained from one assay, without reducing the predictive capacity.