keyword
MENU ▼
Read by QxMD icon Read
search

CYP3A4/5

keyword
https://www.readbyqxmd.com/read/29210320/genetic-variation-in-statin-intolerance-and-a-possible-protective-role-for-ugt1a1
#1
Maria Alice V Willrich, Erin J Kaleta, Sandra C Bryant, Grant M Spears, Laura J Train, Sandra E Peterson, Vanda A Lennon, Stephen L Kopecky, Linnea M Baudhuin
The etiology of statin intolerance is hypothesized to be due to genetic variants that impact statin disposition and clearance. We sought to determine whether genetic variants were associated to statin intolerance. The studied cohort consisted of hyperlipidemic participants (n = 90) clinically diagnosed with statin intolerance by a cardiologist and matched controls without statin intolerance. Creatine kinase activity, lipid profiles and genetic analyses were performed on genes involved in statin metabolism and included UGT1A1 and UGT1A3 sequencing and targeted analyses of CYP3A4*22, CYP3A5*3, SLCO1B1*5 and *1b, ABCB1 c...
December 6, 2017: Pharmacogenomics
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
#2
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/29191071/allosteric-activation-of-cytochrome-p450-3a4-by-efavirenz-facilitates-midazolam-binding
#3
Tomohiko Ichikawa, Hirofumi Tsujino, Takahiro Miki, Masaya Kobayashi, Chiaki Matsubara, Sara Miyata, Taku Yamashita, Kohei Takeshita, Yasushige Yonezawa, Tadayuki Uno
1. The purpose of this study is to investigate the heteroactivation mechanism of CYP3A4 by efavirenz, which enhances metabolism of midazolam in vivo, in terms of its binding to CYP3A4 with in vitro spectroscopic methods. 2. Efavirenz exhibited a type II spectral change with binding to CYP3A4 indicating a possible inhibitor. Although dissociation constant (Kd) was approximated as 550 μM, efavirenz enhanced binding affinity of midazolam as a co-existing drug with an estimated iKd value of 5.6 µM which is comparable to a clinical concentration...
December 1, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29189189/selective-suppression-of-cyp3a4-mrna-and-enzyme-activity-by-epidermal-growth-factor-in-plated-human-hepatocytes
#4
George Zhang, Duan Wang, Thuy Ho, Robert J Clark, David M Stresser
BACKGROUND: Epidermal growth factor (EGF) is a well-known mitogen that has importance in cell proliferation and differentiation. These properties have led to the common use of EGF as an additive to some cell culture media. EGF has been previously shown to modulate constitutive cytochrome P450 (CYP) expression in vitro. OBJECTIVES: To assess the influence of EGF on the basal and induced expression of CYP3A4, CYP1A2 and CYP2B6 in plated human hepatocytes. METHODS: Human hepatocytes from 3 donors were treated with EGF with and without in the presence of positive control inducers...
November 28, 2017: Drug Metabolism Letters
https://www.readbyqxmd.com/read/29184146/2-3-4-5-tetrahydroxystilbene-2-o-%C3%AE-d-glucoside-exacerbates-acetaminophen-induced-hepatotoxicity-by-inducing-hepatic-expression-of-cyp2e1-cyp3a4-and-cyp1a2
#5
Shangfu Xu, Jie Liu, Jingshan Shi, Zhengtao Wang, Lili Ji
Hepatotoxicity induced by medicinal herb Polygonum multiflorum Thunb. attracts wide attention in the world recently. 2,3,4',5-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is a main active compound in Polygonum multiflorum Thunb. This study aims to observe TSG-provided the aggravation on acetaminophen (APAP)-induced hepatotoxicity in mice by inducing hepatic expression of cytochrome P450 (CYP450) enzymes. Serum alanine/aspartate aminotransferase (ALT/AST) analysis and liver histological evaluation showed that TSG (200, 400, 800 mg/kg) exacerbated the hepatotoxicity induced by sub-toxic dose of APAP (200 mg/kg) in mice, but TSG alone had no hepatotoxicity...
November 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29183580/responses-in-reproductive-organs-steroid-hormones-and-cyp450-enzymes-in-female-mongolian-gerbil-meriones-unguiculatus-over-time-after-quinestrol-treatment
#6
Qian-Qian Su, Yi Chen, Jiao Qin, Tong-Liang Wang, De-Hua Wang, Quan-Sheng Liu
The aim of this study was to assess the effects and reversibility of the synthetic estrogen compound, quinestrol, on the reproductive organs, steroid hormones, and drug-metabolizing enzymes CYP3A4 and CYP1A2 in liver and kidney over time after two quinestrol treatments in female Mongolian gerbils (Meriones unguiculatus). Female gerbils were treated with 4mg/kg quinestrol (9 gerbils/group, 3 treated group) (1 control group, 0mg/kg) for 3days and treated again after 25days. Animals were killed for collection of samples at 5, 10 and 15days after the second treatment ending...
November 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/29176011/estimation-of-fractions-metabolized-by-hepatic-cyp-enzymes-using-a-concept-of-inter-system-extrapolation-factors-isefs-a-comparison-with-the-chemical-inhibition-method
#7
Ken-Ichi Umehara, Felix Huth, Helen Gu, Hilmar Schiller, Tycho Heimbach, Handan He
BACKGROUND: For estimation of fractions metabolized (fm) by different hepatic recombinant human CYP enzymes (rhCYP), calculation of inter-system extrapolation factors (ISEFs) has been proposed. METHODS: ISEF values for CYP1A2, CYP2C19 and CYP3A4/5 were measured. A CYP2C9 ISEF was taken from a previous report. Using a set of compounds, fractions metabolized by CYP enzymes (fm,CYP) values calculated with the ISEFs based on rhCYP data were compared with those from the chemical inhibition data...
November 27, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/29155491/variation-in-the-response-of-clozapine-biotransformation-pathways-in-human-hepatic-microsomes-to-cyp1a2-and-cyp3a4-selective-inhibitors
#8
Michael Murray, Wei V Zhang, Robert J Edwards
The atypical antipsychotic agent clozapine (CLZ) is effective in many patients who are resistant to conventional antipsychotic drugs. Cytochromes P450 (CYPs) 1A2 and 3A4 oxidise CLZ to norCLZ and CLZ N-oxide in human liver. Concurrent treatment with inducers and inhibitors of CYP1A2 modulates CLZ elimination that disrupts therapy. Drug-drug interactions involving CYP3A4 are also significant but less predictable. To further characterise the factors underlying these interactions, we used samples from a cohort of human livers to assess variation in CLZ oxidation pathways in relation to intrinsic CYP3A4 and CYP1A2 activities and the effects of the corresponding selective inhibitors ketoconazole (0...
November 20, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29152762/optimizing-lonafarnib-treatment-for-the-management-of-chronic-delta-hepatitis-the-lowr-hdv-1-study
#9
Cihan Yurdaydin, Onur Keskin, Çağdaş Kalkan, Fatih Karakaya, Aysun Çalişkan, Ersin Karatayli, Senem Karatayli, A Mithat Bozdayi, Christopher Koh, Theo Heller, Ramazan Idilman, Jeffrey S Glenn
BACKGROUND AND RATIONALE: In a proof-of-concept (POC) study, the oral prenylation inhibitor lonafarnib (LNF) decreased HDV RNA during 4 weeks of treatment. Here we explored optimal LNF regimens. METHODS: 15 patients (5 groups; 3 per group) completed dosing as follows: 1) LNF 200 mg BID (12 weeks); 2) LNF 300 mg BID (12 weeks); 3) LNF 100 mg TID (5 weeks); 4) LNF 100 mg BID + pegylated interferon alfa (PEG-IFNα) 180 mcg QW (8 weeks); and 5) LNF 100 mg BID + ritonavir (RTV) 100 mg QD (8 weeks)...
November 20, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29137842/comparison-of-pharmacokinetics-of-newly-discovered-aromatase-inhibitors-by-a-cassette-microdosing-approach-in-healthy-japanese-subjects
#10
Hiroyuki Kusuhara, Tadayuki Takashima, Hisako Fujii, Tsutomu Takashima, Masaaki Tanaka, Akira Ishii, Shusaku Tazawa, Kazuhiro Takahashi, Kayo Takahashi, Hidekichi Tokai, Tsuneo Yano, Makoto Kataoka, Akihiro Inano, Suguru Yoshida, Takamitsu Hosoya, Yuichi Sugiyama, Shinji Yamashita, Taisuke Hojo, Yasuyoshi Watanabe
The aim of the present study is to investigate the pharmacokinetics of our newly developed aromatase inhibitors (cetrozole and TMD-322) in healthy subjects by a cassette microdose strategy. A cocktail of cetrozole and TMD-322 was administered intravenously or orally (1.98 μg for each drug) to six healthy volunteers in a crossover fashion. Anastrozole (1.98 μg) was also included in the oral cocktail. Total body clearance and bioavailability were 12.1 ± 7.1 mL/min/kg and 34.9 ± 32.3% for cetrozole, and 16...
September 21, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29134945/drug-drug-interaction-potential-of-the-hepatitis-b-and-hepatitis-d-virus-entry-inhibitor-myrcludex-b-assessed-in-vitro
#11
Antje Blank, Katrin Meier, Stephan Urban, Walter Emil Haefeli, Johanna Weiss
BACKGROUND: Myrcludex B is a first-in-class virus entry inhibitor for patients with chronic hepatitis B or B/D infections. In patients it will be co-administered with drugs needed for the disease or comorbidities. We aimed to define the risk of drug-drug interactions by characterizing the influence of myrcludex B on relevant drug transporting and metabolizing enzymes in vitro. METHODS: Inhibition of P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP/ABCG2), and the organic anion transporting polypeptides 1B1 and 1B3 (OATP1B1/SLCO1B1 and OATP1B3/SLCO1B3) was measured in cells over-expressing the respective transporter using fluorogenic substrates...
November 14, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/29117990/simultaneous-physiologically-based-pharmacokinetic-pbpk-modeling-of-parent-and-active-metabolites-to-investigate-complex-cyp3a4-drug-drug-interaction-potential-a-case-example-of-midostaurin
#12
Helen Gu, Catherine Dutreix, Sam Rebello, Taoufik Ouatas, Lai Wang, Dung Yu Chun, Heidi J Einolf, Handan He
Midostaurin (PKC412) is being investigated for the treatment of acute myeloid leukemia (AML) and advanced systemic mastocytosis (advSM). It is extensively metabolized by cytochrome P450 (CYP) 3A4 to form 2 major active metabolites, CGP52421 and CGP62221. In vitro and clinical drug-drug interaction (DDI) studies indicated that midostaurin and its metabolites are substrates, reversible and time-dependent inhibitors, and inducers of CYP3A4. A simultaneous pharmacokinetic model of parent and active metabolites was initially developed by incorporating data from in vitro, preclinical, and clinical pharmacokinetic studies in healthy volunteers and in patients with AML or advSM...
November 8, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29117640/functional-characterization-of-22-cyp3a4-protein-variants-to-metabolize-ibrutinib-in-vitro
#13
Ren-Ai Xu, Jian Wen, Pengfei Tang, Chenchen Wang, Saili Xie, Bo-Wen Zhang, Quan Zhou, Jian-Ping Cai, Guo-Xin Hu
Cytochrome P450 3A4 (CYP3A4) is quantitatively the most important P450 enzyme in adults. It is suggested that CYP3A4 genetic polymorphisms may influence the rate of the metabolism and elimination of CYP3A4 substrates in humans. Ibrutinib is an anti-cancer drug and primarily metabolized by CYP3A4. The aim of this study was to systematically investigate the effects of 22 CYP3A4 protein variants on the metabolism of ibrutinib in vitro. When compared with wild-type CYP3A4.1, two variants (CYP3A4.17 and CYP3A4.24) had no detectable enzyme activity; five variants (CYP3A4...
November 8, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29105855/dicloxacillin-induces-cyp2c19-cyp2c9-and-cyp3a4-in-vivo-and-in-vitro
#14
Tore Bjerregaard Stage, Magnus Graff, Susan Wong, Louise Ladebo Rasmussen, Flemming Nielsen, Anton Pottegård, Kim Brøsen, Deanna L Kroetz, S Cyrus Khojasteh, Per Damkier
AIM: The aim of this study was to study potential cytochrome P450 induction by dicloxacillin. METHODS: We performed an open-label randomized two-phase 5-drug clinical pharmacokinetic cocktail crossover study in 12 healthy men with and without pretreatment with 1g dicloxacillin three times daily for 10 days. Plasma and urine was collected over 24 hours and the concentration of all five drugs and their primary metabolites was determined using a LC-MS/MS method. Cryopreserved primary human hepatocytes were exposed to dicloxacillin for 48h and changes in gene expression and enzyme activity of CYP3A4, CYP2C9, CYP2B6 and CYP1A2 was investigated...
November 4, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29095797/influence-of-renal-function-on-pharmacokinetics-of-antiepileptic-drugs-metabolized-by-cyp3a4-in-a-patient-with-renal-impairment
#15
Yoshiaki Yamamoto, Naotaka Usui, Takuji Nishida, Miho Mori, Yukitoshi Takahashi, Katsumi Imai, Yoshiyuki Kagawa, Yushi Inoue
BACKGROUND: Several studies have demonstrated that renal impairment not only decreases renal clearance, but also hepatic clearance of medications that are CYP3A4 substrates. We evaluated the influence of renal function on the pharmacokinetics of antiepileptic drugs (AEDs) metabolized by CYP3A4. METHODS: We retrospectively calculated the concentration/dose ratio (CD ratio) for topiramate and clobazam in an epilepsy patient with renal impairment. In addition, we determined the CD ratio of perampanel in 17 patients with normal renal function and compared it with that in the patient with renal impairment...
October 31, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29092680/mass-balance-and-metabolism-of-z-215-a-novel-proton-pump-inhibitor-in-healthy-volunteers
#16
Ryoko Toda, Tomoharu Miyagawa, Yuka Masuda, Yusuke Hoshino, Kazuyoshi Yoshii, Masamichi Hirayama, Minaka Shibuya, Yoshihiro Kawabata
The human mass balance of [(14 )C]Z-215, a novel proton pump inhibitor, was characterised in six healthy male volunteers following single oral administration of [(14 )C]Z-215 (20 mg, 3.7 MBq) to determine the elimination pathway of Z-215 and the distribution of its metabolites in plasma, urine, and faeces (NCT02618629). [(14 )C]Z-215 was rapidly absorbed, with a Cmax of 434 ng/mL at 0.38 h for Z-215 and 732 ng eq./mL at 0.5 h for total radioactivity. Means of 59.61% and 31.36% of the administered radioactive dose were excreted in urine and faeces, respectively, within 168 h post-dose...
November 2, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29081699/optimization-of-antidepressant-use-with-pharmacogenetic-strategies
#17
Clara Torrellas, Juan Carlos Carril, Ramón Cacabelos
BACKGROUND: The response rate in the pharmacological treatment of depression has been estimated to be around 50%, achieving a remission in symptomatology in only one third of the patients. Suboptimal prescription of antidepressants has been proposed as a significant explanatory factor for this therapeutic inefficacy. The use of pharmacogenetic testing might favor the optimization of pharmacotherapy in emotional disorders. However, its implementation in the clinical routine requires studies which prove its efficacy...
October 2017: Current Genomics
https://www.readbyqxmd.com/read/29079874/study-on-the-effect-of-emd386088-a-5-ht6-receptor-partial-agonist-in-enhancing-the-anti-immobility-action-of-some-antidepressants-in-rats
#18
Magdalena Jastrzębska-Więsek, Agata Siwek, Anna Partyka, Marcin Kołaczkowski, Maria Walczak, Magdalena Smolik, Gniewomir Latacz, Katarzyna Kieć-Kononowicz, Anna Wesołowska
The effect of some antidepressants co-administered with EMD386088 in the modified forced swim test in rats was investigated. Additionally, the pharmacokinetics, metabolic stability, and the effect of EMD386088 on P450 cytochromes were determined. Intraperitoneal (i.p.) coadministration of EMD386088 (2.5 mg/kg) and imipramine (15 mg/kg), reboxetine (5 mg/kg), moclobemide (10 mg/kg), or bupropion (10 mg/kg) evoked significant antidepressant-like activity, whereas no effect was observed after joint administration of EMD386088 with s-citalopram (10 mg/kg)...
October 27, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29079577/structural-and-functional-effects-of-cytochrome-b5-interactions-with-human-cytochrome-p450-enzymes
#19
Aaron G Bart, Emily E Scott
The small heme-containing protein cytochrome b5 can facilitate, inhibit, or have no effect on cytochrome P450 catalysis, often in a P450-dependent and substrate-dependent manner that is not well understood. Herein solution NMR was used to identify b5 residues interacting with different human drug-metabolizing P450 enzymes. NMR results revealed that P450 enzymes bound to either b5 α4-5 (CYP2A6 and CYP2E1) or this region and α2-3 (CYP2D6 and CYP3A4) and suggested variation in the affinity for b5 Mutations of key b5 residues suggest that not only are different b5 surfaces responsible for binding different P450 enzymes, but that these different complexes are relevant to the observed effects on P450 catalysis...
October 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29075618/elimination-of-mycoplasma-contamination-from-infected-human-hepatocyte-c3a-cells-by-intraperitoneal-injection-in-balb-c-mice
#20
Jun Weng, Yang Li, Lei Cai, Ting Li, Gongze Peng, Chaoyi Fu, Xu Han, Haiyan Li, Zesheng Jiang, Zhi Zhang, Jiang Du, Qing Peng, Yi Gao
Background/Aims: The use of antibiotics to eliminate Mycoplasma contamination has some serious limitations. Mycoplasma contamination can be eliminated by intraperitoneal injection of BALB/c mice with contaminated cells combined with screening monoclonal cells. However, in vivo passage in mice after injection with contaminated cells requires a long duration (20-54 days). Furthermore, it is important to monitor for cross-contamination of mouse and human cells, xenotropic murine leukemia virus-related virus (XMRV) infection, and altered cell function after the in vivo treatment...
2017: Frontiers in Cellular and Infection Microbiology
keyword
keyword
68093
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"