Read by QxMD icon Read

Drug Metabolism Letters

Sugandha Chaudhari, Shitalkumar Zambad, Mohammed Ali
The intake of complementary and alternative medicines leads to various drug interactions, which may affect pharmacodynamics or pharmacokinetics. This study was conducted to determine the interaction of glipizide (GZ) with an aqueous extract of Azadirachta indica (AZI) leaves. The pharmacokinetics and pharmacodynamics were evaluated through the oral glucose tolerance test, high Fat diet (HFD) and streptozotocin-induced diabetes in Wistar rats. In vitro CYP3A Activity of AZI at 50µg and 100 µg was assessed using liver microsomes...
November 5, 2018: Drug Metabolism Letters
Yildiz Yilmaz, Gareth Williams, Markus Walles, Nenad Manevski, Stephan Krahenbuhl, Gian Camenisch
BACKGROUND: Although the liver is the primary organ of drug metabolism, lungs also contain drug-metabolizing enzymes and may therefore contribute to the elimination of drugs. In this investigation, the precision-cut lung slice (PCLS) technique was standardized with the aims of characterizing and comparing rat and human pulmonary drug metabolizing activity. METHOD: Due to the limited availability of human lung tissue, standardization of the PCLS method was performed with rat lung tissue...
October 22, 2018: Drug Metabolism Letters
Steven X Hu
BACKGROUND: Age has significant impact on activities of hepatic metabolizing enzymes in humans and animals. Flavin-containing monooxygenase (FMO) and aldehyde oxidase are two important hepatic enzymes. Understanding of impact of age on these two enzymes is still limited. This work was to investigate growth impact on hepatic FMO and AO activities in domestic male pigs. METHODS: Porcine liver microsomes and cytosol were prepared from the livers of male domestic pigs at ages of 1 day, 2, 5, 10 and 20 weeks...
September 13, 2018: Drug Metabolism Letters
M Ramesh, Prasad V Bharatam
Diclofenac is a non-steroidal antiinflammatory drug. It is predominantly metabolized by CYP2C9. 4̍-hydroxydiclofenac and its quinoneimine are the metabolites of diclofenac. However, few numbers of serious cases of idiosyncratic hepatotoxicity due to diclofenac metabolism were reported. The formation of the quinoneimine metabolite was found to be responsible for this idiosyncratic toxicity. Quinoneimine is an over-oxidized metabolite of diclofenac. In this work, computational studies were conducted to detail the formation of a quinoneimine metabolite from diclofenac...
September 13, 2018: Drug Metabolism Letters
Albert P Li, Kirsten Amaral, Ming-Chih David Ho
We report here an evaluation of a novel experimental system- cofactor-supplemented permeabilized cryopreserved human enterocytes (MetMax™ cryopreserved human enterocytes (MMHE), patent pending) for applications in the evaluation of enteric drug metabolism. A major advantage of MMHE over conventional cryopreserved human enterocytes (CCHE) is the simplification of the use procedures including storage at -80o C instead of in liquid nitrogen, and use of the cells immediately after thawing without a need for centrifugation and microscopic evaluation of cell density and viability and cell density adjustment...
August 20, 2018: Drug Metabolism Letters
Poonam Giri, Lakshmikant Gupta, Sneha Naidu, Vipul Joshi, Nirmal Patel, Shyamkumar Giri, Nuggehally R Srinivas
BACKGROUND: The use of poly-pharmacy in the present day clinical therapy has made identification of clinical drug-drug interaction risk an important aspect of drug development process. Although many drugs can be metabolized to sulfoxide and/or sulfone metabolites, seldom is known on the CYP inhibition potential and/or the metabolic fate for such metabolites. OBJECTIVE: The key objectives were: a) to evaluate the in vitro CYP inhibition potential of select parent drugs with sulfoxide/sulfone metabolites; b) to assess the in vitro metabolic fate of the same panel of parent drugs and metabolites...
August 16, 2018: Drug Metabolism Letters
William L Fitch, S Cyrus Khojasteh, Ignacio Aliagas, Kevin Johnson
BACKGROUND: There is a continued need for improvements in the efficiency of metabolite structure elucidation. OBJECTIVE: We propose to take LC retention time (RT) into consideration during the process of structure determination. METHOD: Herein we develop a simple methodology that employs a chromatographic hydrophobicity index (CHI) framework for standardizing LC conditions and introduce and utilize the concept of a predictable CHI change upon Phase 1 biotransformation (CHIbt)...
August 1, 2018: Drug Metabolism Letters
Sandra Regina Lepri, Daniele Sartori, Simone Cristine Semprebon, Adrivanio Baranoski, Giuliana Castello Coatti, Mario Sergio Mantovani
• Background: Genistein (5,7-Dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is the most abundant isoflavone in soybean, which has been associated with a lower risk of development of cancer and cardiovascular diseases. Of particular interest regarding cancer preventive properties of flavonoids is their interaction with cytochrome P450 enzymes (CYPs). However, contradictory data report the effect of genistein on expression of СYPs enzymes. • Objective: The aim of this study was to investigate the effects of genistein on cytochrome P450 (CYP) gene expression levels in human hepatocellular carcinoma (HepG2/C3A) and colon adenocarcinoma (HT29) cells...
July 9, 2018: Drug Metabolism Letters
Michael Z Liao, Chunying Gao, Deepak Kumar Bhatt, Bhagwat Prasad, Qingcheng Mao
BACKGROUND: Few studies have systematically investigated pregnancy-induced changes in protein abundance of drug transporters in organs important for drug/xenobiotic disposition. OBJECTIVE: The goal of this study was to compare protein abundance of important drug/xenobiotic transporters including Abcb1a, Abcg2, Abcc2, and Slco1b2 in the liver, kidney and brain of pregnant mice on gestation day 15 to that of non-pregnant mice. METHODS: The mass spectrometry-based proteomics was used to quantify changes in protein abundance of transporters in tissues from pregnant and non-pregnant mice...
June 25, 2018: Drug Metabolism Letters
Mithat Gunduz, Upendra A Argikar, Amanda L Cirello, Jennifer L Dumouchel
BACKGROUND: Acyl glucuronides of xenobiotics have been a subject of wide interest from the pharmaceutical industry with respect biochemical reactivity, hepatic disposition, and enterohepatic circulation. The reactivity and lack of stability of an acyl glucuronide for a clinical candidate could pose major developability concerns. To date, multiple in vitro assays have been published to assess the risk associated with acyl glucuronides. Despite this fact, the translation of these findings to predicting clinical safety remains poor...
June 10, 2018: Drug Metabolism Letters
Emine B Yalcin, Ming Tong, Gina Gallucci, Suzanne M de la Monte
BACKGROUND: The high levels of blood alcohol achieved with chronic plus binge alcohol exposures are somewhat reduced by co-administration of tobacco specific Nicotine-Derived Nitrosamine Ketone (NNK) suggesting that NNK may alter alcohol metabolism. OBJECTIVE: To test this hypothesis, we We examined ethanol and acetaldehyde-metabolizing enzyme activities and malondialdehyde adduct formation in rats exposed to ethanol (chronic + binge), NNK, or both. METHODS: 4-week old Long Evans rats were fed liquid diets containing 0% or 26% caloric ethanol for 8 weeks...
June 10, 2018: Drug Metabolism Letters
Suresh Balani
No abstract text is available yet for this article.
2018: Drug Metabolism Letters
Carolina P Vieira, Daniel V Neves, Eduardo B Coelho, Vera Lucia Lanchote
BACKGROUND: Nebivolol is a drug available as a racemate of d-nebivolol (SRRR) and lnebivolol (RSSS). In human liver microsomes, CYP2D6 mainly catalyses the metabolism of lnebivolol, while CYP2C19 catalyses the metabolism of d-nebivolol. Nebivolol stereoselective pharmacokinetics has been described only for extensive metabolizers (EM). OBJECTIVE: To describe the stereoseletive nebivolol pharmacokinetics in CYP2D6 poor metabolizers (PM) and to assess whether the phenotype has an impact on nebivolol pharmacokinetics...
2018: Drug Metabolism Letters
Wan-Yong Feng, Jenny Wen, Kathe Stauber
BACKGROUND: Recently, it has been an increasing concern on the bioactivation and adverse reactions associated with consumption of herbal and nature products. 7-Ethoxycoumarin is one of coumarin family compounds, but little information is available regarding its potential reactive metabolites. METHOD: 7-ethoxylcoumarin was incubated individually with human, monkey, dog and rat hepatocytes for 2 hr, metabolites were detected, identified and characterized using high resolution liquid chromagraphy - tandem mass spectrometry...
2018: Drug Metabolism Letters
Osama Y Alshogran, Esra A F Al-Obaidi, Belal A Al-Husein, Ashraf O Oweis
BACKGROUND: The nonrenal clearance of drugs mediated by hepatic reduction is selectively altered by kidney disease. This study evaluated the influence of uremic serum on the expression and activity of reductase enzymes. METHODS: Human hepatocellular carcinoma cells (HepG2) were incubated with 5% pooled serum collected from patients with hemodialysis (pre- and post-dialysis session) or control subjects. The mRNA expression of various aldo-keto (AKR1C) and carbonyl (CBR) reductases were measured...
2018: Drug Metabolism Letters
Elena K Schneider
BACKGROUND & OBJECTIVE: Since the release of ivacaftor-lumacaftor, several red-flags have been raised that highlight the clinical efficacy of this combination strategy that may be limited due to antagonistic drug-drug interactions. METHOD: The effect of ivacaftor, its major metabolites M1 and M6, lumacaftor and the novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator tezacaftor at 10 µg/mL on the enzymatic activity of the major xenobiotic metabolizing enzymes CYP1A2 and CYP3A4 as well as the minor enzymes CYP2B6 and CYP2C9 was assayed...
2018: Drug Metabolism Letters
Khondoker Alam, Taleah Farasyn, Kai Ding, Wei Yue
BACKGROUND: Membrane transport protein organic anion transporting polypeptide (OATP) 1B3 mediates the cellular uptake of many clinically important drugs including anti-cancer drugs (e.g., paclitaxel). In addition to the well-recognized hepatic expression and function of OATP1B3 [herein named liver-type (Lt) OATP1B3], OATP1B3 also expresses in cancers and has been postulated to play a role in cancer therapy, presumably by facilitating the influx of anti-cancer drugs. Recently, a cancer type (Ct)-OATP1B3 mRNA variant was identified in colon and lung cancer tissues, which encodes truncated Ct-OATP1B3 with negligible transport activity...
2018: Drug Metabolism Letters
Nur Syukriah Ab Rahman, Fadzilah Adibah Abd Majid, Mohd Effendy Abd Wahid, Ain Nabihah Zainudin, Siti Nurazwa Zainol, Hassan Fahmi Ismail, Tet Soon Wong, Nirbhay Kumar Tiwari, Sanjeev Giri
BACKGROUND: SynacinnTM contains five standardized herbal extracts of Orthosiphon Stamineus (OS), Syzygium polyanthum (SZ), Curcuma xantorrizza (CX), Cinnamomum zeylanicum (CZ) and Andrographis paniculata (AP) and is standardized against phytochemical markers of rosmarinic acid, gallic acid, curcumin, catechin and andrographolide respectively. This herbal medicine has been used as health supplement for diabetes. SynacinnTM is recommended to be consumed as supplement to the diabetic drugs...
2018: Drug Metabolism Letters
Natalia V Mesonzhnik, Natalia E Moskaleva, Ksenia M Shestakova, Ksenya O Kurynina, Pavel A Baranov, Natalia M Gretskaya, Igor V Serkov, Igor I Lyubimov, Vladimir V Bezuglov, Svetlana A Appolonova
BACKGROUND: Nitroproston is a novel prostaglandin-based compound modified by NOdonating groups with potential application in obstructive respiratory diseases such as asthma and obstructive bronchitis. Nitroproston has been extensively studied using various pharmacological models. Its biological stability is still uncertain. OBJECTIVE: The aim of the present study was to evaluate Nitroproston stability in vitro, as well as to identify and characterize its major biodegradation products...
2018: Drug Metabolism Letters
Akira Ogasawara, Nozomu Kato, Nao Torimoto, Fumika Aohara, Rikiya Ohashi, Yasuhiro Yamada, Hideki Taniguchi
BACKGROUND: The HepaRG cells have key drug metabolism functionalities comparable to those of primary human hepatocytes. Many studies have reported that this cell line can be used as a reliable in vitro model for human drug metabolism studies, including the assessment of cytochrome P450 (CYP) induction. OBJECTIVES: The objective of this study is to determine whether CYP mRNA level measurement is superior to the CYP enzyme activity measurement as a convenient high-throughput method for evaluating CYP induction potential using HepaRG cells...
2018: Drug Metabolism Letters
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"