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Drug Metabolism and Drug Interactions

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https://www.readbyqxmd.com/read/25367614/cyp-2c19-and-udp-glucuronosyltransferases-not-only-for-drugs-but-also-for-endobiotics
#1
EDITORIAL
Gérard Siest, Sylvie Fournel-Gigleux, Jacques Magdalou
No abstract text is available yet for this article.
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/25153228/in-vitro-inhibitory-effects-of-herbal-supplements-on-tamoxifen-and-irinotecan-metabolism
#2
Fran Grappe, Gwen Nance, Lori Coward, Greg Gorman
BACKGROUND: As the use of herbal supplements continues to rise throughout the world, the potential for drug-herbal interactions also increases. For chemotherapeutic prodrugs, this interaction could prevent the metabolic conversion of the prodrug to its active metabolite(s), thereby potentially resulting in subtherapeutic systemic exposure of the drug and reduced efficacy of the therapy. METHODS: In this study, in vitro metabolism with human liver microsomes is used to measure the impact of ten commonly used herbal supplements on the biotransformation of the chemotherapeutic prodrugs tamoxifen (TAM) and irinotecan (IR)...
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/25029082/effect-of-silymarin-pretreatment-on-the-bioavailability-of-domperidone-in-healthy-human-volunteers
#3
Shravan Kumar Yamsani, Madhusudan Rao Yamsani
BACKGROUND: The aim of this study was to investigate the effect of silymarin pretreatment on domperidone oral bioavailability in humans. METHODS: The rats were pretreated with silymarin for 7 days. The transport of domperidone across the rat intestine (duodenum, jejunum, ileum, and colon) was studied by using in vitro everted and non-everted sac methods. Samples were collected at preset time points and replaced with buffer. The drug content in the samples was estimated...
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/24995404/systems-medicine-in-the-era-of-big-data-a-game-changer-for-personalized-medicine
#4
EDITORIAL
Ndeye Coumba Ndiaye
No abstract text is available yet for this article.
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/24988246/the-pharmacogenetics-of-carboxylesterases-ces1-and-ces2-genetic-variants-and-their-clinical-effect
#5
REVIEW
Zahra Merali, Stephanie Ross, Guillaume Paré
Human carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2) are serine esterases responsible for the hydrolysis of ester and amide bonds present in a number of pharmaceutical products. Several common genetic variants of the CES1 and CES2 genes have been shown to influence drug metabolism and clinical outcomes. Polymorphisms of the CES1 gene have been reported to affect the metabolism of dabigatran etexilate, methylphenidate, oseltamivir, imidapril, and clopidogrel, whereas variants of the CES2 gene have been found to affect aspirin and irinotecan...
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/24870608/effect-of-selective-cyclooxygenase-2-inhibitor-lumiracoxib-on-phenolsulfonphthalein-disposition-in-rats
#6
Hiroaki Honjo, Yuichi Uwai, Tomohiro Nabekura
Selective cyclooxygenase-2 inhibitor lumiracoxib was shown to have the strong inhibitory potencies on the renal organic anion transporter (OAT)1 and also on OAT3 from drug transport experiments. The purpose of this study was to examine the effect of lumiracoxib on disposition of phenolsulfonphthalein (PSP) - which is mainly excreted into urine via OATs - from in vivo experiments. After the intravenous injection of PSP and lumiracoxib into rats, pharmacokinetic analysis was performed. After the intravenous injection of PSP as a bolus, its plasma concentration decreased time-dependently...
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/24867283/pharmacogenetics-in-jewish-populations
#7
REVIEW
Yao Yang, Inga Peter, Stuart A Scott
Spanning over 2000 years, the Jewish population has a long history of migration, population bottlenecks, expansions, and geographical isolation, which has resulted in a unique genetic architecture among the Jewish people. As such, many Mendelian disease genes and founder mutations for autosomal recessive diseases have been discovered in several Jewish groups, which have prompted recent genomic studies in the Jewish population on common disease susceptibility and other complex traits. Although few studies on the genetic determinants of drug response variability have been reported in the Jewish population, a number of unique pharmacogenetic variants have been discovered that are more common in Jewish populations than in other major racial groups...
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/24825095/lurasidone-drug-drug-interaction-studies-a-comprehensive-review
#8
REVIEW
Yu-Yuan Chiu, Larry Ereshefsky, Sheldon H Preskorn, Nagaraju Poola, Antony Loebel
BACKGROUND: To evaluate potential drug-drug interactions with the atypical antipsychotic lurasidone. METHODS: Seven phase I studies were conducted to investigate the effects of repeated dosing of ketoconazole, diltiazem, rifampin, or lithium on the pharmacokinetics (PK) of single oral doses of lurasidone, or the effects of repeated dosing of lurasidone on the PK of digoxin, midazolam, or the oral contraceptive norgestimate/ethinyl estradiol. Two 6-week, phase III studies included evaluation of the potential for interaction between lurasidone and lithium or valproate...
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/24825094/molecular-functionality-of-cyp2c9-polymorphisms-and-their-influence-on-drug-therapy
#9
REVIEW
Yazun Bashir Jarrar, Su-Jun Lee
CYP2C9 metabolizes approximately 20% of clinically used drugs, including the narrow therapeutic window drugs warfarin and phenytoin. More than 16,000 variants have been reported in the National Center for Biotechnology Information CYP2C9 database, as well as 58 alleles in the official P450 Nomenclature Committee website. Two single nucleotide polymorphisms represented by the CYP2C9*2 and CYP2C9*3 alleles have been studied extensively. However, in addition to these two alleles, other genetic factors and an individual's biological characteristics contribute to the overall drug phenotype...
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/24807167/inhibition-of-oatp-1b1-and-oatp-1b3-by-tyrosine-kinase-inhibitors
#10
Varun Khurana, Mukul Minocha, Dhananjay Pal, Ashim K Mitra
BACKGROUND: The potential of tyrosine kinase inhibitors (TKIs) interacting with other therapeutics through hepatic uptake transporter inhibition has not been fully delineated in drug-drug interactions (DDIs). This study was designed to estimate the half-maximal inhibitory concentration (IC50) values of five small-molecule TKIs (pazopanib, nilotinib, vandetanib, canertinib and erlotinib) interacting with organic anion-transporting polypeptides (OATPs): OATP-1B1 and -1B3. METHODS: The IC50 values of TKIs and rifampicin (positive control) were determined by concentration-dependent inhibition of TKIs on cellular accumulation of radiolabeled probe substrates [3H]estrone sulfate and [3H]cholecystokinin octapeptide...
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/24756056/importance-of-abc-transporters-in-different-tissues
#11
EDITORIAL
Umashankar Vetrivel, Gurunathan Subramanian
No abstract text is available yet for this article.
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/24756055/frequency-of-cyp450-enzyme-gene-polymorphisms-in-the-greek-population-review-of-the-literature-original-findings-and-clinical-significance
#12
REVIEW
Georgia Ragia, Efstathia Giannakopoulou, Makrina Karaglani, Ioanna-Maria Karantza, Anna Tavridou, Vangelis G Manolopoulos
The cytochrome P450 (CYP450) enzyme family is involved in the oxidative metabolism of many therapeutic drugs and various endogenous substrates. These enzymes are highly polymorphic. Prevalence of CYP450 enzyme gene polymorphisms vary among different populations and substantial inter- and intra-ethnic variability in frequency of CYP450 enzyme gene polymorphisms has been reported. This paper provides an overview and investigation of CYP450 genotypic and phenotypic reports published in the Greek population.
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/24744305/pharmacogenetics-of-drug-metabolizing-enzymes-in-brazilian-populations
#13
REVIEW
Alvaro Cerda, Mario Hiroyuki Hirata, Rosario Dominguez Crespo Hirata
Phase I and II drug metabolizing enzymes (DMEs) play an important role in biotransformation of endogenous and exogenous compounds including drugs currently used in pharmacoterapy. Moreover, the genetic variability of DMEs causes important interindividual differences in drug and metabolite exposure, drug response, and risk of adverse drug reactions. We reviewed pharmacogenetics/pharmacogenomics (PGx) studies that evaluated the influence of polymorphisms in the CYPs genes - mainly CYP1, CYP2 and CYP3 gene families - and in the phase II genes - TPMT, NAT2, GSTs and UGTs - on therapeutic response in Brazilian cohorts...
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/24643911/the-effect-of-ast-120-on-the-single-dose-pharmacokinetics-of-metoprolol-extended-release-tablets-in-healthy-subjects
#14
RANDOMIZED CONTROLLED TRIAL
Shinsuke Inoue, Miho Shimizu, Kiyoshi Arita, Kei Akimoto
BACKGROUND: This was a randomized, open-label, three-way crossover study to assess the effects of AST-120 (an orally administered spherical carbon adsorbent acting in the gastrointestinal tract without systemic circulation) on the single-dose pharmacokinetics of metoprolol in an extended-release formulation (metoprolol ER) in healthy volunteers. METHODS: A total of 34 subjects were singly administered metoprolol ER alone (A), and metoprolol ER in combination with AST-120 simultaneously (B) and 1 h later (C)...
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/24643910/role-of-oatp-1b1-and-or-oatp-1b3-in-hepatic-disposition-of-tyrosine-kinase-inhibitors
#15
Varun Khurana, Mukul Minocha, Dhananjay Pal, Ashim K Mitra
BACKGROUND: The metabolism of tyrosine kinase inhibitors (TKIs) is mainly mediated via hepatic route, but the mechanism responsible for their hepatocellular accumulation is still unknown. This study was designed to understand the contribution of organic anion transporting polypeptides (OATPs) in the hepatic uptake of selected TKIs - pazopanib, canertinib, erlotinib, vandetanib and nilotinib. METHODS: Michaelis-Menten (MM) kinetic parameters for TKIs were determined by concentration-dependent cellular accumulation of selected TKIs using Chinese hamster ovary cells - wild type as well as transfected with humanized OATP-1B1 and OATP-1B3 transporter proteins...
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/24615483/raloxifene-pharmacodynamics-is-influenced-by-genetic-variants-in-the-rankl-rank-opg-system-and-in-the-wnt-signaling-pathway
#16
Simona Mencej-Bedrač, Janja Zupan, Simona Jurković Mlakar, Andrej Zavratnik, Janez Preželj, Janja Marc
BACKGROUND: Raloxifene is a selective estrogen receptor (ER) modulator (SERM) used for the treatment of osteoporosis. However, its efficacy and also its safety vary greatly among treated patients, and it might be influenced by the individuals' genetic background. As the receptor activator of the nuclear factor κB (RANK) ligand (RANKL)/RANK/osteoprotegerin (OPG) system is essential for osteoclastogensis and Wnt signaling pathway for osteoblastogenesis, we decided to evaluate the raloxifene treatment in regard to selected polymorphisms in key genes of these two main bone regulatory pathways...
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/24607919/venlafaxine-pharmacokinetics-focused-on-drug-metabolism-and-potential-biomarkers
#17
REVIEW
Paulo Magalhães, Gilberto Alves, Adrián Llerena, Amílcar Falcão
Venlafaxine (VEN) is one of the safest and most effective drugs used in the treatment of selective serotonin reuptake inhibitors-resistant depression, and thereby it is nowadays one of the most commonly prescribed antidepressants. Nevertheless, patients treated with antidepressant drugs including VEN have exhibited large inter-individual variability in drug outcomes, possibly due to the influence of genetic and nongenetic factors on the drug pharmacokinetics and/or pharmacodynamics. Among them, an increased interest has emerged over the last few years on the genetic and/or phenotypic profile for drug-metabolizing cytochrome P450 isoenzymes and drug transporters such as potential predictive pharmacokinetic-based biomarkers of the variability found in drug biodisposition and antidepressant response...
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/24598833/liver-enzyme-abnormalities-during-antipsychotic-treatment-a-case-report-of-risperidone-associated-hepatotoxicity
#18
Enrique López-Torres, Agnes Süveges, Eva M Peñas-LLedó, Alvaro Doña, Pedro Dorado, Adrián LLerena, Roland Berecz
BACKGROUND: Drug-induced liver enzyme abnormalities may indicate hepatic injury. Antipsychotic drugs also may cause increase in the liver enzymes and serum bilirubin levels. The present report evaluates the case of a patient with risperidone-associated hepatocellular damage. CASE SUMMARY: A 19-year-old Caucasian man was admitted to the Department of Psychiatry with paranoid schizophrenia and risperidone was administered in a gradually increasing dose up to 8 mg/day...
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/24558228/characterization-of-abc-transporters-in-human-skin
#19
Hanan Osman-Ponchet, Anais Boulai, Magali Kouidhi, Karine Sevin, Marion Alriquet, Alexandre Gaborit, Béatrice Bertino, Pierre Comby, Bernard Ruty
BACKGROUND: Most identified drug transporters belong to the ATP-binding cassette (ABC) and solute carrier (SLC) families. Recent research indicates that these transporters play an important role in the absorption, distribution and excretion of drugs, and are involved in clinically relevant drug-drug interactions for systemic drugs. However, very little is known about the role of drug transporters in human skin, especially in the disposition of topically applied drugs, and their involvement in drug-drug interactions...
2014: Drug Metabolism and Drug Interactions
https://www.readbyqxmd.com/read/24468612/potential-pharmacokinetic-interactions-of-therapeutic-cytokines-or-cytokine-modulators-on-small-molecule-drugs-mechanistic-understanding-via-studies-using-in-vitro-systems
#20
REVIEW
Jin Zhou, Feng Li
The potential pharmacokinetic interactions between macromolecules and small-molecule drugs have received more and more attention with the increasing development of macromolecule therapeutics. Studies have shown that cytokines can differentially modulate drug-metabolizing enzymes and transporters, which raises concerns on the potential interactions of therapeutic cytokines and cytokine modulators on the disposition of small-molecule drugs. Although many in vitro studies have been conducted to characterize the effects of cytokines on drug-metabolizing enzymes and transporters, these studies were limited to only a handful of cytokines, such as interleukin-1 (IL-1), IL-6, tumor necrosis factor-α, and interferon...
2014: Drug Metabolism and Drug Interactions
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