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 parameters and genetic factors, which explain 50% of the variability in EFV PK parameters. The most relevant associations for metabolizing enzymes were found in CYP2B6 (rs3745274), in agreement with previous studies. The influence of transporters on the kinetics of EFV was also proved with significant correlations between the PK parameters of EFV and MRP4 (rs1751034, rs2274407). Analysis of gene-gene interactions with CYP2B6 was particularly useful to reinforce the role of MRP4 and to reveal unknown associations, such as that of DRD3. However, the role of DRD3 cannot be a direct effect but an indirect one due to physical proximity of NAT and the DRD3 locus in the genome.

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

doi

10.1016/j.dmpk.2016.06.001

subject

Has Abstract

pub_date

2016-10-01 00:00:00

pages

349-355

issue

5

eissn

1347-4367

issn

1880-0920

pii

S1347-4367(16)30030-1

journal_volume

31

pub_type

杂志文章
  • 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

  • Valproic acid transport in the choriocarcinoma placenta cell line JEG-3 proceeds independently of the proton-dependent transporters MCT1 and MCT4.

    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

    pub_type: 杂志文章

    doi:10.1016/j.dmpk.2018.03.004

    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

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

    abstract::The current EMA drug interaction guideline was published in 2012. This guideline gives important recommendations on the information required to elucidate the interaction potential of an investigational drug, both as effects of the investigational drug on the PK of other drugs and effects of other medicinal products on...

    journal_title:Drug metabolism and pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.1016/j.dmpk.2019.11.005

    authors: Cole S,Kerwash E,Andersson A

    更新日期:2020-02-01 00:00:00

  • New SRM data dependent exclusion (MS)n measurement for structural determination of drug metabolites using LC/ESI/Ion trap MS.

    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

    pub_type: 杂志文章

    doi:10.2133/dmpk.18.390

    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

  • Bioinformatics research on inter-racial difference in drug metabolism II. Analysis on relationship between enzyme activities of CYP2D6 and CYP2C19 and their relevant genotypes.

    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

    pub_type: 杂志文章

    doi:10.2133/dmpk.18.71

    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

  • 6-Hydroxyindole is an endogenous long-lasting OATP1B1 inhibitor elevated in renal failure patients.

    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

    pub_type: 杂志文章

    doi:10.1016/j.dmpk.2020.09.001

    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

  • The effects of N-glycosylation on the glucuronidation of zidovudine and morphine by UGT2B7 expressed in HEK293 cells.

    abstract::UDP-glucuronosyltransferases (UGTs) are glycoproteins in endoplasmic reticulum membranes. UGT2B7 is an important UGT isoenzyme expressed in human liver and glucuronidates various endogenous and exogenous substances. Although this enzyme has three potential N-glycosylation sites (asparagine at positions 67, 68 and 315)...

    journal_title:Drug metabolism and pharmacokinetics

    pub_type: 杂志文章

    doi:10.2133/dmpk.dmpk-11-rg-135

    authors: Nagaoka K,Hanioka N,Ikushiro S,Yamano S,Narimatsu S

    更新日期:2012-01-01 00:00:00

  • Relationship between the plasma fentanyl and serum 4β-hydroxycholesterol based on CYP3A5 genotype and gender in patients with cancer pain.

    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

    pub_type: 杂志文章

    doi:10.1016/j.dmpk.2016.04.001

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

    更新日期:2016-06-01 00:00:00

  • 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

  • Nonlinear pharmacokinetics of aprindine in guinea pigs.

    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

    pub_type: 杂志文章

    doi:10.2133/dmpk.17.292

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

    更新日期:2002-01-01 00:00:00

  • Co-administration of tacrolimus suppresses pharmacokinetic modulation of multiple subcutaneously administered human interferon-alpha in Beagle dogs.

    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

    pub_type: 杂志文章

    doi:10.2133/dmpk.25.149

    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

  • 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

  • Na+/H+ exchanger 3 affects transport property of H+/oligopeptide transporter 1.

    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

    pub_type: 杂志文章

    doi:10.2133/dmpk.20.443

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

    更新日期:2005-12-01 00:00:00

  • The roles of nuclear receptors CAR and PXR in hepatic energy metabolism.

    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

    pub_type: 杂志文章,评审

    doi:10.2133/dmpk.23.8

    authors: Konno Y,Negishi M,Kodama S

    更新日期:2008-01-01 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

  • 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

  • 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

  • Enhanced uptake of glycerol by butyrate treatment in HCT-15 human colon cancer cell line.

    abstract::The HCT-15 human colon cancer cell line has a Na(+)-dependent carrier-mediated transport system for the uptake of glycerol. A similar transport system has been suggested to be present also in the small intestine and is of interest with regard to its role in the absorption of glycerol and possibly some structurally rel...

    journal_title:Drug metabolism and pharmacokinetics

    pub_type: 杂志文章

    doi:10.2133/dmpk.22.195

    authors: Fujimoto N,Inoue K,Ohgusu Y,Hayashi Y,Yuasa H

    更新日期:2007-06-01 00:00:00

  • Population pharmacokinetics of valsartan in pediatrics.

    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

    pub_type: 杂志文章,多中心研究

    doi:10.2133/dmpk.24.145

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

    更新日期:2009-01-01 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

  • Induction of hepatic cytochrome P450s by the herbal medicine Sophora flavescens extract in rats: impact on the elimination of theophylline.

    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

    pub_type: 杂志文章

    doi:10.2133/dmpk.dmpk-10-rg-055

    authors: Ueng YF,Tsai CC,Lo WS,Yun CH

    更新日期:2010-01-01 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 hydrocotarnine on cytochrome P450 and P-glycoprotein.

    abstract::The injectable form of oxycodone contains hydrocotarnine that is supposed to potentiate the analgesic effect of oxycodone with unknown mechanism(s). In this study, the effects of hydrocotarnine on the cytochrome P450 (CYP) and P-glycoprotein (P-gp) were investigated. Hydrocotarnine did not induce a significant change ...

    journal_title:Drug metabolism and pharmacokinetics

    pub_type: 杂志文章

    doi:10.2133/dmpk.24.108

    authors: Ito K,Kubota Y,Toda T,Suto S,Ikarashi N,Sugiyama K

    更新日期:2009-01-01 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

  • Pharmacokinetics and bioavailability of oral single-dose maleic acid in biofluids of Sprague-Dawley rats.

    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

    pub_type: 杂志文章

    doi:10.1016/j.dmpk.2016.09.005

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

    更新日期:2016-12-01 00:00:00

  • Trimethylamine N-oxygenation in cynomolgus macaques genotyped for flavin-containing monooxygenase 3 (FMO3).

    abstract::Polymorphic human and cynomolgus macaque flavin-containing monooxygenases (FMO) 3 are important oxygenation enzymes for nitrogen-containing drugs. Inter-animal variability of FMO3-dependent drug oxygenations in vivo is suspected in cynomolgus macaques because such variability is evident in humans. Therefore, this foll...

    journal_title:Drug metabolism and pharmacokinetics

    pub_type: 杂志文章

    doi:10.1016/j.dmpk.2020.07.001

    authors: Shimizu M,Uno Y,Utoh M,Yamazaki H

    更新日期:2020-12-01 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

  • Structure-activity relationship modeling for predicting interactions with pregnane X receptor by recursive partitioning.

    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

    pub_type: 杂志文章

    doi:10.2133/dmpk.dmpk-11-rg-159

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

    更新日期:2012-01-01 00:00:00

  • Population pharmacokinetic analysis of a novel muscarinic receptor antagonist, imidafenacin, in healthy volunteers and overactive bladder patients.

    abstract::The objectives of this study were to develop a population pharmacokinetic model of imidafenacin and to explore the factors that affect the pharmacokinetics of imidafenecin. A total of 2406 plasma samples were collected from 90 healthy volunteers and 457 patients with overactive bladder. We determined the plasma concen...

    journal_title:Drug metabolism and pharmacokinetics

    pub_type: 杂志文章

    doi:10.2133/dmpk.23.456

    authors: Ohno T,Nakade S,Nakayama K,Kitagawa J,Miyabe H,Konomi T,Miyata Y

    更新日期:2008-01-01 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