Effect of CAR polymorphism on the pharmacokinetics of artemisinin in healthy Chinese subjects.

Abstract:

:Repeated pretreatment with the antimalarial drug artemisinin (QHS) could lead to reduced exposure to the parent drug, which is mainly mediated by auto-induction of CYP2B6 activity. CYP2B6 is most sensitive to the inductive effect of constitutive androstane receptor (CAR), which can be activated by QHS. CYP2B6 polymorphism has no influence on pharmacokinetics of QHS derivatives. This study aimed to investigate the effect of CAR (C540T) polymorphism on the auto-induction metabolism-mediated pharmacokinetics of QHS. Healthy Chinese subjects (six in each group with the genotypes of CAR 540C/C, 540C/T and 540T/T; all carrying the CYP2B6*1*1 genotype) received a recommended two-day oral doses of QHS-piperaquine (PQ) to assess the pharmacokinetics of QHS and its metabolite deoxyartemisinin (DQHS). The exposures to QHS and DQHS were significantly lower (p < 0.05) in subjects homozygous for the CAR 540T/T genotype than those with the 540C/C genotype after the repeated dose. QHS did not show different induction clearance in subjects homozygous for the 540C/C genotype (1.3-fold), compared with those carrying the heterozygous 540C/T (2.1-fold) or homozygous 540T/T (1.7-fold) genotype. In conclusion, the CAR (C540T) genotype contributed to the interindividual variability of QHS pharmacokinetics, and the dose regimen for QHS deserves further evaluation especially in specific populations.

authors

Zang M,Zhao L,Zhu F,Li X,Yang A,Xing J

doi

10.1016/j.dmpk.2014.10.008

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

123-6

issue

1

eissn

1347-4367

issn

1880-0920

pii

S1347-4367(14)00017-2

journal_volume

30

pub_type

临床试验,杂志文章
  • Pharmacokinetics and bioavailability of tuftsin-derived T peptide, a promising antitumor agent, in beagles.

    abstract::Tuftsin, a natural phagocytosis-stimulating tetrapeptide, had aroused much interest in tumor immunotherapy, but the poor pharmacokinetics hampered its clinical developments, for that it was extremely susceptible to degradation by enzymolysis in vivo. T Peptide (TP) was a newly designed tuftsin derivative aimed to enha...

    journal_title:Drug metabolism and pharmacokinetics

    pub_type: 杂志文章

    doi:10.1016/j.dmpk.2015.08.005

    authors: Gu R,He Y,Han S,Yuan S,An Y,Meng Z,Zhu X,Gan H,Wu Z,Li J,Zheng Y,Zhang L,Gao L,Dou G

    更新日期:2016-02-01 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

  • 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

  • Genetic variations and haplotypes of CYP2C19 in a Japanese population.

    abstract::Forty-eight single nucleotide variations, including 27 novel ones, were found in the 5'- regulatory region, all of the exons and their surrounding introns of CYP2C19 in 253 Japanese subjects (134 diabetic patients and 119 healthy volunteers). Identified novel variations were as follows: -2772G>A, 2767_-2760delGGTGAACA...

    journal_title:Drug metabolism and pharmacokinetics

    pub_type: 杂志文章

    doi:10.2133/dmpk.20.300

    authors: Fukushima-Uesaka H,Saito Y,Maekawa K,Ozawa S,Hasegawa R,Kajio H,Kuzuya N,Yasuda K,Kawamoto M,Kamatani N,Suzuki K,Yanagawa T,Tohkin M,Sawada J

    更新日期:2005-08-01 00:00:00

  • Physiologically-based modeling of monoclonal antibody pharmacokinetics in drug discovery and development.

    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

    pub_type: 杂志文章,评审

    doi:10.1016/j.dmpk.2018.11.002

    authors: Glassman PM,Balthasar JP

    更新日期:2019-02-01 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

  • 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

  • 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

  • Metabolism of selegiline hydrochloride, a selective monoamine b-type inhibitor, in human liver microsomes.

    abstract::The participation of cytochrome P-450 (CYP) isoforms in the metabolism of selegiline was investigated. Experiments using recombinant CYP isoforms expressed in human lymphoblastoid cells showed CYP2B6 to be the major CYP isoform involved with the metabolism of selegiline. CYP1A2 and CYP3A4 also contributed to the metab...

    journal_title:Drug metabolism and pharmacokinetics

    pub_type: 杂志文章

    doi:10.2133/dmpk.17.199

    authors: Kamada T,Chow T,Hiroi T,Imaoka S,Morimoto K,Ohde H,Funae Y

    更新日期:2002-01-01 00:00:00

  • P-glycoprotein limits the brain penetration of olopatadine hydrochloride, H1-receptor antagonist.

    abstract::Olopatadine, a new second-generation antihistamine, is widely used in the treatment of allergic disorders. The low levels of histamine H1 receptor occupancy in human brain by olopatadine, which is related to its minimal sedation, suggest its low penetration into the brain. The present study evaluates the impact of P-g...

    journal_title:Drug metabolism and pharmacokinetics

    pub_type: 杂志文章

    doi:10.2133/dmpk.23.106

    authors: Mimura N,Nagata Y,Kuwabara T,Kubo N,Fuse E

    更新日期:2008-01-01 00:00:00

  • Novel multiple assessment of hepatocellular drug disposition in a single packaged procedure.

    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

    pub_type: 杂志文章

    doi:10.1016/j.dmpk.2015.12.001

    authors: Takahashi R,Ichikawa H,Kanda K

    更新日期:2016-04-01 00:00:00

  • The population genetics of pharmacogenomics VIP variants in the Sherpa population.

    abstract::Polymorphic distributions of pharmacogenes among some ethnicities are under-represented in current pharmacogenetic research. Particularly, there is a paucity of pharmacogenetic information in the Sherpa population in Tibet. We used the Sequenom MassARRAY single nucleotide polymorphism (SNP) genotyping technology to de...

    journal_title:Drug metabolism and pharmacokinetics

    pub_type: 杂志文章

    doi:10.1016/j.dmpk.2015.11.007

    authors: Wang L,Ren Y,Shi X,Yuan D,Liu K,Geng T,Li G,Kang L,Jin TB

    更新日期:2016-02-01 00:00:00

  • Analysis of hepatic disposition of native and galactosylated polyethylenimine complexed with plasmid DNA in perfused rat liver.

    abstract::We studied the intrahepatic disposition characteristics of galactosylated polyethylenimine (Gal-PEI)/plasmid DNA (pDNA) complexes using rat liver perfusion experiment. After intraportal administration, transfection activity in liver of Gal-PEI complexes was approximately 26-fold higher than that of native PEI complexe...

    journal_title:Drug metabolism and pharmacokinetics

    pub_type: 杂志文章

    doi:10.2133/dmpk.18.230

    authors: Fumoto S,Kawakami S,Ishizuka M,Nishikawa M,Yamashita F,Hashida M

    更新日期:2003-01-01 00:00:00

  • A randomized, placebo-controlled, single ascending-dose study to assess the safety, tolerability, pharmacokinetics, and immunogenicity of subcutaneous tralokinumab in Japanese healthy volunteers.

    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

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.dmpk.2017.12.001

    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

  • A novel approach to the prediction of drug-drug interactions in humans based on the serum incubation method.

    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

    pub_type: 杂志文章

    doi:10.2133/dmpk.23.328

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

    更新日期:2008-01-01 00:00:00

  • The influence of aged garlic extract on the uptake of saquinavir and darunavir into HepG2 cells and rat liver slices.

    abstract::Bioavailability and therapeutic outcome of treatment with HIV-protease inhibitors depends on intestinal and hepatic transporter-enzyme interplay. Liver transport of HIV protease inhibitors (saquinavir, darunavir) was assessed in the presence of aged garlic extract, because the HIV-infected often consume garlic supplem...

    journal_title:Drug metabolism and pharmacokinetics

    pub_type: 杂志文章

    doi:10.2133/dmpk.25.307

    authors: Berginc K,Trontelj J,Kristl A

    更新日期:2010-01-01 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

  • Comparison of cytochrome P450 3A enzymes in cynomolgus monkeys and humans.

    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

    pub_type: 杂志文章

    doi:10.2133/dmpk.dmpk-10-nt-022

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

    更新日期:2010-01-01 00:00:00

  • Association of hemoglobin levels, CYP3A5, and NR1I3 gene polymorphisms with tacrolimus pharmacokinetics in liver transplant patients.

    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

    pub_type: 杂志文章

    doi:10.2133/dmpk.dmpk-13-rg-095

    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

  • 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

  • Numerical analysis of apparent decitabine uptake in HCT116 cells: Incorporation of a bidirectional first-order kinetic parameter for ENT1 transport and Michaelis-Menten parameters for subsequent phosphorylation.

    abstract::Decitabine (DAC), a DNA methylation inhibitor, is transported into cancer cells mainly via equilibrative nucleoside transporter 1 (ENT1) and subsequently phosphorylated by deoxycytidine kinase (dCK). We previously reported that apparent DAC uptake into cells may be described using a simple compartment model with clear...

    journal_title:Drug metabolism and pharmacokinetics

    pub_type: 杂志文章

    doi:10.1016/j.dmpk.2019.10.002

    authors: Ueda K,Nakamura T,Tanaka S,Hosokawa M,Iwakawa S,Ogawara KI

    更新日期:2020-02-01 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

  • Synthesis and evaluation of nevirapine analogs to study the metabolic activation of nevirapine.

    abstract::Nevirapine (NVP) is widely used as a non-nucleoside reverse transcriptase inhibitor of HIV-1, however, it is associated with severe skin and liver injury. The mechanisms of these adverse reactions are not yet clear, but the metabolic activation of NVP is thought to be related to the injury process. Until now, several ...

    journal_title:Drug metabolism and pharmacokinetics

    pub_type: 杂志文章

    doi:10.1016/j.dmpk.2020.01.006

    authors: Tateishi Y,Ohe T,Yasuda D,Takahashi K,Nakamura S,Kazuki Y,Mashino T

    更新日期:2020-04-01 00:00:00

  • Paroxetine decreased plasma exposure of glyburide partly via inhibiting intestinal absorption in rats.

    abstract::Accumulating evidences have shown that diabetes is often accompanied with depression, thus it is possible that oral antidiabetic agent glyburide and antidepressive agent paroxetine are co-administered in diabetic patients. The aim of this study was to assess interactions between glyburide and paroxetine in rats. Effec...

    journal_title:Drug metabolism and pharmacokinetics

    pub_type: 杂志文章

    doi:10.1016/j.dmpk.2015.02.004

    authors: Jiang S,Zhao W,Chen Y,Zhong Z,Zhang M,Li F,Xu P,Zhao K,Li Y,Liu L,Liu X

    更新日期:2015-06-01 00:00:00

  • Population pharmacokinetic and exposure-response analyses of guanfacine in Japanese pediatric ADHD patients.

    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

    pub_type: 杂志文章

    doi:10.1016/j.dmpk.2019.07.001

    authors: Tsuda Y,Matsuo Y,Matsumoto S,Wajima T

    更新日期:2019-12-01 00:00:00

  • Decreased expression of intestinal P-glycoprotein increases the analgesic effects of oral morphine in a streptozotocin-induced diabetic mouse model.

    abstract::Morphine is one of the strongest analgesics and is commonly used for the treatment of chronic pain. The pharmacokinetic properties of morphine are, in part, modulated by P-glycoprotein (P-gp). We previously reported that intestinal P-gp expression levels are influenced via the activation of inducible nitric oxide synt...

    journal_title:Drug metabolism and pharmacokinetics

    pub_type: 杂志文章

    doi:10.2133/dmpk.dmpk-11-rg-051

    authors: Nawa A,Fujita-Hamabe W,Kishioka S,Tokuyama S

    更新日期:2011-01-01 00:00:00

  • Evaluation of blood-brain barrier transporters by co-culture of brain capillary endothelial cells with astrocytes.

    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

    pub_type: 杂志文章

    doi:10.2133/dmpk.17.34

    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

  • 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

  • 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

  • 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