keyword
MENU ▼
Read by QxMD icon Read
search

CYP2C8.3

keyword
https://www.readbyqxmd.com/read/29345044/preclinical-characterisation-of-absorption-distribution-metabolism-and-excretion-properties-of-tak-063
#1
Kimio Tohyama, Miyako Sudo, Akio Morohashi, Suguru Kato, Junzo Takahashi, Yoshihiko Tagawa
TAK-063 is currently being developed to treat schizophrenia. In this study, we investigated the absorption, distribution, metabolism and excretion (ADME) properties of TAK-063 using several paradigms. Following oral administration of TAK-063 at 0.3 mg/kg, bioavailability of TAK-063 was 27.4% in rats and 49.5% in dogs with elimination half-lives of 3.1 hr in rats and 3.7 hr in dogs. TAK-063 is a highly permeable compound without P-glycoprotein (P-gp) or breast cancer resistance protein substrate liability and can be readily absorbed into systemic circulation via the intestine...
January 17, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29320899/in-vitro-analysis-of-itraconazole-cis-diastereoisomers-inhibition-of-nine-cytochrome-p450-enzymes-stereoselective-inhibition-of-cyp3a
#2
Kristyna Krasulova, Zdenek Dvorak, Pavel Anzenbacher
Itraconazole (ITZ), an antifungal azole derivate is a chiral drug that consists of four cis-diastereoisomers ((+)-2R,4S,2'R-ITZ-A; (+)-2R,4S,2'S-ITZ-B; (-)2S,4R,2'S-ITZ-C and (-) 2S,4R,2'R-ITZ-D) which may differ in their pharmacokinetics and pharmacodynamics. As itraconazole is known as a CYP3A4 inhibitor causing severe drug-drug interaction, the inhibitory potencies of its individual optical isomers towards nine drug-metabolising cytochrome P450 (including CYP3A, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1), were investigated...
January 10, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29297772/assessment-of-drug-drug-interaction-potential-and-pbpk-modeling-of-cc-223-a-potent-inhibitor-of-the-mammalian-target-of-rapamycin-kinase
#3
Zeen Tong, Rangaraj Narayanan, Christian Atsriku, Jim Nissel, Yan Li, Hong Liu, Xiaomin Wang, Sekhar Surapaneni
1. CC-223 was studied in vitro for metabolism and drug-drug interactions (DDI), and in clinic for interaction with ketoconazole. 2. In vitro, human metabolites of CC-223 included O-desmethyl CC-223 (M1), keto (M2), N-oxide (M3), and imine (M13), with M1 being the most prominent metabolite. 3. CC-223 was metabolized by CYP2C9 and CYP3A, while metabolism of M1 was mediated by CYP2C8 and CYP3A. Ketoconazole increased CC-223 and M1 exposure by 60-70% in healthy volunteers. 4. CC-223 (IC50 ≥ 27 µM) and M1 (IC50 ≥ 46 µM) were inhibitors of CYP2C9 and CYP2C19 in human liver microsomes...
January 3, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29297729/direct-and-quantitative-evaluation-of-the-major-human-cyp-contribution-fmcyp-to-drug-clearance-using-the-in-vitro-silensomes%C3%A2-model
#4
Yannick Parmentier, Corinne Pothier, Nicky Hewitt, Ludwig Vincent, Fabrice Caradec, Jia Liu, Feifei Lin, Marie-Michèle Trancart, Fabrice Guillet, Belkacem Bouaita, Christophe Chesne, Bernard Walther
1. We have applied the concept of using MBIs to produce CYP-Silensomes to quantify the contribution of the major CYPs to drug metabolism (fmCYP). 2. The target CYPs were extensively and selectivity inhibited by the selected MBIs, while non-target CYPs were inhibited by less than 20% of the homologous control activities. Only CYP2D6-Silensomes exhibited a CYP2B6 inhibition that could be easily and efficiently encountered by subtracting the fmCYP2B6 measured using CYP2B6-Silensomes to adjust the fmCYP2D6. 3. To validate the use of a panel of 6 CYP-Silensomes, we showed that the fmCYP values of mono- and multi-CYP metabolised drugs were well predicted, with 70% within ± 15% accuracy...
January 3, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29247736/metabolic-pathway-of-icotinib-in-vitro-the-differential-roles-of-cyp3a4-cyp3a5-and-cyp1a2-on-potential-pharmacokinetic-drug-drug-interaction
#5
TianHong Zhang, KeRong Zhang, Li Ma, Zheng Li, Juan Wang, YunXia Zhang, Chuang Lu, MingShe Zhu, XiaoMei Zhuang
Icotinib is the self-developed small molecule drug in China for targeted therapy of non-small-cell lung cancer. To date, systematic studies on the pharmacokinetic drug-drug interaction (DDI) of icotinib were limited. By identifying metabolite generation in human liver microsomes (HLM) and revealing the contributions of major CYPs in the formation of major metabolites, the aim of the present work is to understand the mechanisms underlying pharmacokinetic and pharmacological variability in clinic. A LC/UV/HRMS method was developed to characterize the icotinib metabolites...
December 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29218011/pharmacogenetic-variation-in-over-100-genes-in-patients-receiving-acenocumarol
#6
Vanessa Gonzalez-Covarrubias, Javier Urena-Carrion, Beatriz Villegas-Torres, J Eduardo Cossío-Aranda, Sergio Trevethan-Cravioto, Raul Izaguirre-Avila, O Javier Fiscal-López, Xavier Soberon
Coumarins are widely prescribed worldwide, and in Mexico acenocumarol is the preferred form. It is well known that despite its efficacy, coumarins show a high variability for dose requirements. We investigated the pharmacogenetic variation of 110 genes in patients receiving acenocumarol using a targeted NGS approach. We report relevant population differentiation for variants on CYP2C8, CYP2C19, CYP4F11, CYP4F2, PROS, and GGCX, VKORC1, CYP2C18, NQO1. A higher proportion of novel-to-known variants for 10 genes was identified on 41 core pharmacogenomics genes related to the PK (29), PD (3), of coumarins, and coagulation proteins (9) including, CYP1A1, CYP3A4, CYP3A5, and F8, and a low proportion of novel-to-known variants on CYP2E1, VKORC1, and SULT1A1/2...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29205295/protein-abundance-of-clinically-relevant-drug-metabolizing-enzymes-in-the-human-liver-and-intestine-a-comparative-analysis-in-paired-tissue-specimens
#7
M Drozdzik, D Busch, J Lapczuk, J Müller, M Ostrowski, M Kurzawski, S Oswald
The work revises and complements existing findings on the distribution of drug metabolizing enzymes' in the first-pass effect organs. We explored gene expression (qPCR) and protein abundance (LC-MS/MS) of CYP1A2, CYP2B6, CYP2C8/9/19, CYP2D6, CYP2E1, CYP3A4/5, UGT1A1/3, UGT2B7/15 in the liver, duodenum, jejunum, ileum and colon in paired tissues from 9 organ donors. All proteins were detected in the liver, but in the intestine CYP2C9/19, CYP2D6, CYP3A4/5, UGT1A1/3 and UGT2B7 were found. CYP3A4 showed comparable abundance in the liver and jejunum, whereas other enzymes were markedly higher in the hepatic tissue...
December 5, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29166542/identification-of-cytochrome-p450-cyp-isoforms-involved-in-the-metabolism-of-artocarpin-and-assessment-of-its-drug-drug-interaction-ddi
#8
Wei Qu, Xuezheng Liu
Artocarpin isolated from an agricultural plant Artocarpus communis has shows anti-inflammation and anticancer activities. In this study, we utilized recombinant human UDP-glucuronosyltransferasesupersomes (UGTs) and human liver microsomes (HLMs) to explore its inhibitory effect on UGTs and cytochrome p450 enzymes(CYPs). Chemical inhibition studies and screening assays with recombinant human CYPs were used to identify if CYP isoform is involved in artocarpin metabolism. Artocarpin showed strong inhibition against UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B7, CYP2C8 and CYP3A4...
November 22, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29163177/assessment-of-pharmacogenomic-panel-assay-for-prediction-of-taxane-toxicities-preliminary-results
#9
Raffaele Di Francia, Luigi Atripaldi, Salvo Di Martino, Carla Fierro, Tommaso Muto, Anna Crispo, Sabrina Rossetti, Gaetano Facchini, Massimiliano Berretta
Backbone: Paclitaxel and docetaxel are the primary taxane anticancer drugs regularly used to treat, breast, gastric, ovarian, head/neck, lung, and genitourinary neoplasm. Suspension of taxane treatments compromising patient benefits is more frequently caused by peripheral neuropathy and allergy, than to tumor progression. Several strategies for preventing toxicity have been investigated so far. Recently, findings on the genetic variants associated with toxicity and resistance to taxane-based chemotherapy have been reported...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29043584/determination-of-the-human-cytochrome-p450-monooxygenase-catalyzing-the-enantioselective-oxidation-of-2-2-3-5-6-pentachlorobiphenyl-pcb-95-and-2-2-3-4-4-5-6-heptachlorobiphenyl-pcb-183
#10
Haruna Nagayoshi, Kensaku Kakimoto, Yoshimasa Konishi, Keiji Kajimura, Takeshi Nakano
2,2',3,5',6-Pentachlorobiphenyl (PCB 95) and 2,2',3,4,4',5',6-heptachlorobiphenyl (PCB 183) possess axial chirality and form the aS and aR enantiomers. The enantiomers of these congeners have been reported to accumulate in the human body enantioselectively via unknown mechanisms. In this study, we determined the cytochrome P450 (CYP) monooxygenase responsible for the enantioselective oxidization of PCB 95 and PCB 183, using a recombinant human CYP monooxygenase. We evaluated 13 CYP monooxygenases, namely CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2E1, CYP2J2, CYP3A4, CYP3A5, CYP4F2, and aromatase (CYP19), and revealed that CYP2A6 preferably oxidizes aS-PCB 95 enantioselectively; however, it did not oxidize PCB 183...
October 17, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29022765/polymorphisms-in-genes-involved-in-vasoactive-eicosanoid-synthesis-affect-cardiovascular-risk-in-renal-transplant-recipients
#11
Guillermo Gervasini, Enrique Luna, Guadalupe Garcia-Pino, Lilia Azevedo, Sonia Mota-Zamorano, Juan José Cubero
OBJECTIVE: Arachidonic acid metabolism by cytochrome P450 (CYP) epoxygenases leads to epoxyeicosatrienoic acids (EETs), which are eicosanoids with vasodilator and anti-inflammatory properties. We aim to determine whether genetic variability in these routes may contribute to cardiovascular (CV) risk in renal transplant recipients. METHODS: In a cohort of 355 patients, we determined the presence of two polymorphisms, CYP2C8*3 and CYP2J2*7, known to affect eicosanoid levels...
November 8, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28944677/multiplex-and-label-free-relative-quantification-approach-for-studying-protein-abundance-of-drug-metabolizing-enzymes-in-human-liver-microsomes-using-swath-ms
#12
Rohitash Jamwal, Benjamin J Barlock, Sravani Adusumalli, Ken Ogasawara, Brigitte L Simons, Fatemeh Akhlaghi
We describe a sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS) based method for label-free, simultaneous, relative quantification of drug metabolism enzymes in human liver microsomes (HLM; n = 78). In-solution tryptic digestion was aided by a pressure cycling method, which allowed a 90 min incubation time, a significant reduction over classical protocols (12-18 h). Digested peptides were separated on an Acquity UHPLC Peptide BEH C18 column using a 60 min gradient method at a flow rate of 0...
October 10, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28893623/cyp17a1-inhibitor-abiraterone-an-anti-prostate-cancer-drug-also-inhibits-the-21-hydroxylase-activity-of-cyp21a2
#13
Jana Malikova, Simone Brixius-Anderko, Sameer S Udhane, Shaheena Parween, Bernhard Dick, Rita Bernhardt, Amit V Pandey
Abiraterone is an inhibitor of CYP17A1 which is used for the treatment of castration resistant prostate cancer. Abiraterone is known to inhibit several drug metabolizing cytochrome P450 enzymes including CYP1A2, CYP2D6, CYP2C8, CYP2C9, CYP2C19, CYP3A4 and CYP3A5, but its effects on steroid metabolizing P450 enzymes are not clear. In preliminary results, we had observed inhibition of CYP21A2 by 1μM abiraterone. Here we are reporting the effect of abiraterone on activities of CYP21A2 in human adrenal cells as well as with purified recombinant CYP21A2...
November 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28740425/efficacy-of-piroxicam-for-postoperative-pain-after-lower-third-molar-surgery-associated-with-cyp2c8-3-and-cyp2c9
#14
Adriana Maria Calvo, Paulo Zupelari-Gonçalves, Thiago José Dionísio, Daniel Thomas Brozoski, Flávio Augusto Faria, Carlos Ferreira Santos
OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are metabolized by the cytochrome P450 enzymes (CYPs), predominantly CYP2C8 and CYP2C9. The aim of this study was to evaluate the possible association of polymorphisms in the CYP2C8*3 and CYP2C9 genes with the clinical efficacy of oral piroxicam (20 mg daily for 4 days) after lower third molar surgeries with regard to postoperative pain, swelling, trismus, adverse reactions, need for rescue medication and the volunteer's overall satisfaction...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28730856/in-vitro-drug-drug-interactions-of-budesonide-inhibition-and-induction-of-transporters-and-cytochrome-p450-enzymes
#15
Nancy Chen, Donghui Cui, Qing Wang, Zhiming Wen, Richard D Finkelman, Devin Welty
1. Budesonide is a glucocorticoid used in the treatment of several respiratory and gastrointestinal inflammatory diseases. Glucocorticoids have been demonstrated to induce cytochrome P450 (CYP) 3A and the efflux transporter P-glycoprotein (P-gp). This study aimed to evaluate the potential of budesonide to act as a perpetrator or a victim of transporter- or CYP-mediated drug-drug interactions (DDIs). 2. In vitro studies were conducted for P-gp, breast cancer resistance protein and organic anion and cation transporters (OATP1B1, OATP1B3, OAT1, OAT3, OCT2) in transporter-transfected cells...
July 21, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28715853/effect-of-gemfibrozil-and-rifampicin-on-the-pharmacokinetics-of-selexipag-and-its-active-metabolite-in-healthy-subjects
#16
Shirin Bruderer, Marc Petersen-Sylla, Margaux Boehler, Tatiana Remeňová, Atef Halabi, Jasper Dingemanse
AIMS: Based on in vitro data, there is evidence to suggest that cytochrome P450 (CYP) 2C8 is involved in the metabolism of selexipag and its active metabolite, ACT-333679. The present study evaluated the possible pharmacokinetic interactions of selexipag with gemfibrozil, a strong CYP2C8 inhibitor, and rifampicin, an inducer of CYP2C8. METHODS: The study consisted of two independent parts, each conducted according to an open-label, randomized, crossover design. The pharmacokinetics and safety of selexipag and ACT-333679 were studied following single-dose administration either alone or in the presence of multiple-dose gemfibrozil (part I) or rifampicin (part II) in healthy male subjects...
July 17, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28686288/distribution-of-cyp2c8-and-cyp2c9-amino-acid-substitution-alleles-in-south-indian-diabetes-patients-a-genotypic-and-computational-protein-phenotype-study
#17
Durga Koteswara Rao, Dwaraknath K Murthy, Nazia Sultana Shaik, Babajan Banaganapalli, Kumaraswami Konda, Hanmantha P Rao, Eswar Ganti, Zuhair Ahmed Awan, Ashraf A El-Harouni, Ramu Elango, Imran Ali Khan, Noor Ahmad Shaik
The CYP2C8 and CYP2C9 are two major isoforms of the cytochrome P450 enzyme family, which is involved in drug response, detoxification, and disease development. This study describes the differential distribution of amino acid substitution variants of CYP2C8 (*2-I269F & *3-R139K) and CYP2C9 (*2-C144R & *3-L359A) genes in 234 type 2 diabetes mellitus (T2DM) patients and 218 healthy controls from Andhra Pradesh, South India. Single locus genotype analysis has revealed that homozygous recessive genotypes of 2C8*2-TT (P ≤ ...
July 7, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28674251/co-administration-of-fluvastatin-and-cyp3a4-and-cyp2c8-inhibitors-may-increase-the-exposure-to-fluvastatin-in-carriers-of-cyp2c9-genetic-variants
#18
Yuji Mukai, Masayuki Narita, Erika Akiyama, Kanami Ohashi, Yasutaka Horiuchi, Yuka Kato, Takaki Toda, Anders Rane, Nobuo Inotsume
Fluvastatin, which is one of the hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins), is primarily metabolized by CYP2C9 and to a lesser extent by CYP3A4 and CYP2C8. Predictions of drug-drug interactions (DDI) are important for the safety of combination therapies with statins, in particular drugs that are metabolized by CYP3A4. Little information is available regarding drug interactions with fluvastatin. Since CYP2C9 is a polymorphic enzyme, we investigated the effect of DDI via CYP2C9, CYP3A4, and CYP2C8 on fluvastatin pharmacokinetics by using a validated prediction method in relation to CYP2C9 variants...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28657402/in-vitro-evaluation-of-the-inhibition-and-induction-potential-of-olaparib-a-potent-poly-adp-ribose-polymerase-inhibitor-on-cytochrome-p450
#19
Alex McCormick, Helen Swaisland, Venkatesh Pilla Reddy, Maria Learoyd, Graeme Scarfe
1. In vitro studies were conducted to evaluate potential inhibitory and inductive effects of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, on cytochrome P450 (CYP) enzymes. Inhibitory effects were determined in human liver microsomes (HLM); inductive effects were evaluated in cultured human hepatocytes. 2. Olaparib did not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2D6 or CYP2E1 and caused slight inhibition of CYP2C9, CYP2C19 and CYP3A4/5 in HLM up to a concentration of 100 µM. However, olaparib (17‒500 µM) inhibited CYP3A4/5 with an IC50 of 119 µM...
June 28, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28600193/functional-and-molecular-responses-of-the-blue-mussel-mytilus-edulis-hemocytes-exposed-to-cadmium-an-in%C3%A2-vitro-model-and-transcriptomic-approach
#20
Philippine Granger Joly de Boissel, Michel Fournier, Juan Carlos Rodriguez-Lecompte, Patty McKenna, Frederick Kibenge, Ahmed Siah
The bivalve mollusk, Mytilus edulis, is used as a sentinel species in several monitoring programs due to its ability to bio-accumulate contaminants. Its immune system consists of hemocytes and humoral components, which constitute the main part of the hemolymph. The present study is aimed at understanding the effects of Cd on the differentially expressed genes involved in the phagocytosis of M. edulis' hemocytes. Our approach focuses on an in vitro model by exposing hemocytes to different concentrations of Cd ranging from 10(-9) M to 10(-3) M...
August 2017: Fish & Shellfish Immunology
keyword
keyword
27757
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"