Genotoxicity of 4-(piperazin-1-yl)-8-(trifluoromethyl)pyrido[2,3-e][1,2,4] triazolo[4,3-a]pyrazine, a Potent H4 Receptor Antagonist for the Treatment of Allergy: Evidence of Glyoxal Intermediate Involvement
Conclusion: In the present investigation, a novel method was developed to trap glyoxal, which may potentially be liberated from piperazine moiety. These findings led to modifications on the piperazine ring to mitigate the bioactivation pathways leading to mutagenicity. Subsequently, the next generation compounds with modified piperazine moiety, retained H4R inhibitory potency in vitro and were not genotoxic in the Ames mutagenicity assay. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - February 8, 2018 Category: Drugs & Pharmacology Source Type: research

Evaluation of Farnesoid X Receptor Target Gene Induction in Human Hepatocytes: Amino Acid Conjugation
Conclusion: In conclusion, there appears to be some species differences in the activation of FXR target genes. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - February 8, 2018 Category: Drugs & Pharmacology Source Type: research

Transactivation Assays that Identify Indirect and Direct Activators of Human Pregnane X Receptor (PXR, NR1I2) and Constitutive Androstane Receptor (CAR, NR1I3)
Conclusion: Cell based transactivation assays employing the full-length receptors and native promoters identify both direct and indirect activators of either or both human PXR and CAR. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - February 8, 2018 Category: Drugs & Pharmacology Source Type: research

Selective Suppression of CYP3A4 mRNA and Enzyme Activity by Epidermal Growth Factor in Plated Human Hepatocytes
Conclusion: Because of the larger effect on the basal CYP3A4 compared to the induced response, EGF as a media additive enables a higher dynamic range in a CYP3A4 induction assay, potentially expanding the range of donor hepatocytes suitable for use in induction studies. These findings also suggest that EGF may be an important regulator of CYP3A4 expression in vivo. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - February 8, 2018 Category: Drugs & Pharmacology Source Type: research

The Effects of Drug Metabolizing Enzyme Inhibitors on Hepatic Efflux and Uptake Transporters
Conclusion: ABT, pargyline, allopurinol and methimazole have no inhibitory effects on the studied ABC and SLC transporters, suggesting the inhibitors are unlikely to cause confounding inhibition of transporters when used in metabolism studies. However, SKF525A, menadione, raloxifene and piperine can inhibit the activities of ABC and/or SLC transporters. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - February 8, 2018 Category: Drugs & Pharmacology Source Type: research

Investigation of Ocular Bioactivation Potential and the Role of Cytochrome P450 2D Enzymes in Rat
Conclusion: This study also indicates that in vitro hepatic metabolism is over-predictive of ocular metabolism following topically ocular dosed timolol. The research, herein, highlights the eye as an organ capable of first pass metabolism for topical drugs. Thus, new ophthalmologic considerations for studying and designing long term topical therapies in preclinical species are needed in drug discovery. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - February 8, 2018 Category: Drugs & Pharmacology Source Type: research

A Pharmacokinetic-Pharmacodynamic Model of Tamoxifen and Endoxifen to Predict Their Distribution and Effects on Inhibition of Tumor Growth
Conclusion: We established a PK-PD model of tamoxifen and endoxifen to predict the tumor growth. The parameters of the pharmacodynamic model, which characterized the tumor growth, revealed the patterns of tamoxifen's anti-tumor functions. The PK-PD model successfully provided illustration for the pharmacokinetics of tamoxifen and endoxifen, and predicted the inhibition effect of endoxifen on the tumor growth. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - February 8, 2018 Category: Drugs & Pharmacology Source Type: research

Analysis of Elevated Levels of Nandrolone Decanoate Induced Cytochrome- P450 Alterations in Mice
Background: Frequent recreational use of Anabolic Androgenic Steroids (AAS) is an instance of substance abuse which mimics the status of a natural hormone and upon prolonged exposure may lead to adverse drug reactions. These adverse drug reactions proceed in a manner so as to alter the normal metabolism of an enzyme mediated pathway such as the Cytochrome P450 (CYP) family of enzymes. Objective: The present study was conducted to investigate the impact of overuse of Nandrolone Decanoate (ND), an AAS, upon CYP enzyme activity and a CYP gene, belonging to CYP1 family. Methods: The study was carried out using normal and ND tr...
Source: Drug Metabolism Letters - February 8, 2018 Category: Drugs & Pharmacology Source Type: research

Therapeutic Potentials and Cytochrome P450-Mediated Interactions Involving Herbal Products Indicated for Diabetes Mellitus
Conclusion: The literature abounds with reports on the utilization of herbal medications for the treatment of diabetes mellitus since time immemorial, but very few of these herbal products have undergone clinical trials. Also, studies on the herb-drug interactions were limited. Due to the complex phytochemical composition of the herbs, concomitant administration with conventional drugs resulted in alterations of pharmacological effects of some drugs. Evidences of beneficial interactions were identified for medical exploitation. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - February 8, 2018 Category: Drugs & Pharmacology Source Type: research

Meet Our Editorial Board Member
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - February 8, 2018 Category: Drugs & Pharmacology Source Type: research

Effects of Fenofibrate on the Expression of Small Heterodimer Partner (SHP) and Cytochrome P450 (CYP) 2D6
Conclusion: These results indicate that fenofibrate has minimal effects on CYP2D6 expression despite increased SHP expression. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 17, 2017 Category: Drugs & Pharmacology Source Type: research

Gender Difference of Hepatic and Intestinal CYP3A4 in CYP3AHumanized Mice Generated by a Human Chromosome-engineering Technique
Conclusion: These findings suggest that the expression and activity levels of CYP3A4 in the liver are higher in females than in males, whereas there is no gender difference in the levels in the intestine of CYP3A-HAC mice. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 17, 2017 Category: Drugs & Pharmacology Source Type: research

Potential Minor Haplotypes of CYP2D6 in the Japanese Population
Conclusion: Using a large database of CYP2D6 genotypes in the Japanese population, we found a novel haplotype which involves 100C>T without 4180G>C. Although the haplotype will need to be confirmed by full sequencing, it may be a unique haplotype with an exception to the strong linkage disequilibrium between 100C>T and 4180G>C. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 17, 2017 Category: Drugs & Pharmacology Source Type: research

Inhibitory Effect of Fruit Juices on the Doxorubicin Metabolizing Activity of Carbonyl Reductase 1
Conclusion: An apple juice and a grape fruit juice showed strong inhibitory effects on doxorubicin metabolism by CBR1 in vitro. These results suggest that the intake of flavonoid-containing juices can be a promising measure for protection against doxorubicin-induced cardiac toxicity, enabling patients to keep higher adherence with routine use in light of safety, economic performance and stable supply to market. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 17, 2017 Category: Drugs & Pharmacology Source Type: research

Quantification of Sulfotransferases 1A1 and 1A3/4 in Tissue Fractions and Cell Lines by Multiple Reaction Monitoring Mass Spectrometry
Background: Within the sulfotransferase (SULT) superfamily of metabolic enzymes, SULT1A1 and 1A3/4 isoforms are of particular interest, due to their abilities to catalyze the sulfation of phenolic endobiotics and xenobiotics. Although the difference in their substrate specificity is well documented, an isoform-specific quantification method is still not available. Objective: To detect and quantify SULT1A1 and 1A3/4 in S9 fractions and cell lines using targeted mass spectrometry-based proteomics. Method: Samples were tryptically digested, and signature peptides were quantified using liquid chromatography- multiple reaction ...
Source: Drug Metabolism Letters - November 17, 2017 Category: Drugs & Pharmacology Source Type: research

The Role of Placental Carbonyl Reducing Enzymes in Biotransformation of Bupropion and 4-methylnitrosamino-1-(3-pyridyl)-1-butanone
Background: Bupropion (BUP) has a potential to be an effective pharmacotherapy for smoking cessation during pregnancy. Smoking during pregnancy stimulates placental carbonyl reductases that catalyze the biotransformation of BUP. 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) is a potent carcinogen of cigarette smoke. Carbonyl reduction of NNK into 4- methylnitrosamino-1-(3-pyridyl)-1-butanol (NNAL) constitutes a major step in NNK detoxification. Thus, placentas of pregnant smokers on BUP therapy can become a site of drug-drug interaction. Therefore, we investigated the effect of continuous exposure to BUP and cigarette...
Source: Drug Metabolism Letters - November 17, 2017 Category: Drugs & Pharmacology Source Type: research

Mixed Matrix Method Provides A Reliable Metabolite Exposure Comparison for Assessment of Metabolites in Safety Testing (MIST)
Conclusion: Quantitative assessment of metabolite coverage in safety species can be made using mixed matrix method with similar accuracy and scientific rigor to those obtained from validated bioanalytical methods. Moving forward, we are encouraging the industry and regulators to consider accepting the mixed matrix method for assessing metabolite exposure comparisons between humans and animal species used in toxicology studies. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 17, 2017 Category: Drugs & Pharmacology Source Type: research

Metabolic Profile of Flunitrazepam: Clinical and Forensic Toxicological Aspects
Conclusion: It is aimed that knowing the metabolism of FNZ may lead to the development of new analytical strategies for early detection, since this drug is typically present in very low concentrations in blood and urine when used to facilitate sexual assault. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 17, 2017 Category: Drugs & Pharmacology Source Type: research

Obesity and Inflammation and Altered Clopidogrel Pharmacokinetics and Pharmacodynamics
Conclusion: Comprehensive understanding of the mechanisms underlying obesity-related high onclopidogrel platelet reactivity will help in the optimization of antithrombotic therapy in this patient population. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 17, 2017 Category: Drugs & Pharmacology Source Type: research

Preface
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 17, 2017 Category: Drugs & Pharmacology Source Type: research

Meet Our Editorial Board Member
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 17, 2017 Category: Drugs & Pharmacology Source Type: research

Acknowledgements to reviewers
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - March 15, 2017 Category: Drugs & Pharmacology Source Type: research

The Metabolism of Methazolamide in Immortalized Human Keratinocytes, HaCaT Cells
Conclusion: N-[3-methyl-5-sulfo-1,3,4-thiadiazol-2(3H)-ylidene]acetamide (MSO) is not considered to be a direct product of an enzymatic reaction, but rather an auto-oxidation product of N-[3-methyl-5- sulfe-1,3,4-thiadiazol-2(3H)-ylidene]acetamide, a chemically unstable sulfenic acid, which is produced by cytochrome P450 from the -lyase product of cysteine conjugate of methazolamide. MSO is considered to be susceptible to glutathione and to return to glutathione conjugate of methazolamide, forming a futile cycle. A hypothetical scenario is presented as to the onset of the disease. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - March 15, 2017 Category: Drugs & Pharmacology Source Type: research

Quantification of Etodolac in Human Plasma for Pharmacokinetics and Bioequivalence Studies in 27 Korean Subjects
Conclusion: Thus, the new testified method was successfully applied for the pharmacokinetic and bioequivalence studies for two etodolac formulations. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - March 15, 2017 Category: Drugs & Pharmacology Source Type: research

Variability of Zaleplon 5-Oxidase Activity in Mice and Humans, and Inhibition by Raloxifene
Conclusion: High inter-individual variability of ZAL 5-oxidase activity and potential for interaction of ZAL with other medicines that are inhibitors of aldehyde oxidase should be taken into consideration in clinical usage of ZAL. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - March 15, 2017 Category: Drugs & Pharmacology Source Type: research

Ortho-Methylarylamines as Time-Dependent Inhibitors of Cytochrome P450 1A1 Enzyme
Conclusion: Four compounds have been identified that exhibit selective time-dependent inhibition of P450 1A1. Modeling studies have indicated that the proximity of the aromatic methyl group to the heme-Fe could be the main contributor for time-dependent inhibition. Future studies will focus on the confirmation of the involvement of the aromatic methyl group in enzyme inactivation. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - March 15, 2017 Category: Drugs & Pharmacology Source Type: research

A Novel Liquid Chromatography Tandem Mass Spectrometry Method for the Estimation of Bilirubin Glucuronides and its Application to In Vitro Enzyme Assays
Conclusion: We have developed a sensitive LC-MS/MS based method for the quantitation of bilirubin and its glucuronides from in vitro incubations. This method was successfully utilized to determine bilirubin glucuronidation kinetics in HLM and human rUGT1A1. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - March 15, 2017 Category: Drugs & Pharmacology Source Type: research

Genipin Inhibits the Induction of Inducible Nitric Oxide Synthase Through the Inhibition of NF-κB Activation in Rat Hepatocytes
Conclusion: Genipin influenced the induction of inflammatory mediators, iNOS and TNF-α, in part through the inhibition of NF-κB activation in hepatocytes. Genipin may have therapeutic potential for organ injuries including liver. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - March 15, 2017 Category: Drugs & Pharmacology Source Type: research

Strong Induction of Cytochrome P450 1A/3A, But not P450 2B, in Cultured Hepatocytes from Common Marmosets and Cynomolgus Monkeys by Typical Human P450 Inducing Agents
Conclusion: These results indicate that P450 1A/3A induction by typical human P450 inducers in hepatocytes from marmosets and/or cynomolgus monkeys are similar to those of humans (except for P450 2B induction by phenobarbital in humans), suggesting that marmosets and cynomolgus monkeys might be suitable models for evaluating the drug interactions in preclinical studies. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - March 15, 2017 Category: Drugs & Pharmacology Source Type: research

Cytochrome P450 2A6 Phenotyping Using Dietary Caffeine Salivary Metabolite Ratios and Genotyping Using Blood on Storage Cards in Non-smoking Japanese Volunteers
Background: A simple method of genotyping and phenotyping cytochrome P450 2A6 (CYP2A6) was previously reported using individual blood samples and urinary caffeine metabolite ratios of 1,7-dimethyluric acid (17U) to 1-methylxanthine (1X). Objective: Blood spotted onto storage cards and salivary caffeine metabolites were analyzed in 27 healthy non-smoking Japanese volunteers with no prior abstention from dietary caffeine intake. Methods: 1,7-Dimethylxanthine (17X), 17U, 1X, and caffeine levels in spot saliva samples were determined in Japanese non-smokers by high-performance liquid chromatography under normal dietary caffein...
Source: Drug Metabolism Letters - March 15, 2017 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics, Metabolism and Disposition of [14C]XQ-1H After Intravenous Administration to Male Rats
Conclusion: Binding of XQ to RBCs may lower the blood’s viscosity and thus provide symptomatic improvement of ischemic stroke patients. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - March 15, 2017 Category: Drugs & Pharmacology Source Type: research

Meet Our Editorial Board Member
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - March 15, 2017 Category: Drugs & Pharmacology Source Type: research

Effect of Cardiovascular Injury on Catabolism of Adenosine and Adenosine 5-‘Triphosphate in Systemic Blood in a Freely Moving Rat Model In Vivo
Background: Previous studies have shown that catabolism of adenosine 5’-triphosphate (ATP) in red blood cell (RBC) may be a key factor for cardiovascular protection and maintaining cardiovascular homeostasis. Objective: To investigate the effect of cardiovascular injury on adenosine and ATP catabolism in systemic blood using a freely moving rat model in vivo. Method: After acclimatized to the experimental environment, Sprague Dawley (SD) rats were each given either isoproterenol (30 mg/kg) or saline (1 mL/kg) by subcutaneous (sc) injection. Blood samples were collected sequentially for up to 6 hours for measurement o...
Source: Drug Metabolism Letters - October 1, 2016 Category: Drugs & Pharmacology Source Type: research

CYP2B6 and OPRM1 Receptor Polymorphisms at Methadone Clinics And Novel OPRM1 Haplotypes: A Cross-Sectional Study
Conclusion: C64T and G15631T in CYP2B6and G31A, G691C, and A118G in OPRM1were found to be polymorphic. The new haplotypes may give a new insight on methadone clinics. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - October 1, 2016 Category: Drugs & Pharmacology Source Type: research

UHPLC Quantitation Method for New Thiazolidinedione LPSF/GQ-02 and In Vitro/In Vivo Kinetic Studies
Conclusion: The intravenous pharmacokinetic parameters are in agreement with a good future posology, even though the plasma concentrations from oral administration were not quantifiable in a dose of 12 mg/kg. The preliminary safety study demonstrated no acute effect of the drug in liver and kidneys. The LPSF/GQ-02 is a new thiazolidinedione that should continue being evaluated for future clinical use. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - October 1, 2016 Category: Drugs & Pharmacology Source Type: research

Identification and Characterization of the Human Cytosolic Sulfotransferases Mediating the Sulfation of Clioquinol and Iodoquinol
Conclusion: Collectively, these results provided a molecular basis underling the metabolism of clioquinol and iodoquinol through sulfation. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - October 1, 2016 Category: Drugs & Pharmacology Source Type: research

Inhibition of Procarcinogen Activating Enzyme CYP1A2 Activity and Free Radical Formation by Caffeic Acid and its Amide Analogues
Conclusion: From our results, caffeic acid and its amide analogues are in vitro inhibitors of human CYP1A2 catalytic activity and free radical formation. They may be useful to be developed as potential chemopreventive agents that block CYP1A2-mediated chemical carcinogenesis. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - October 1, 2016 Category: Drugs & Pharmacology Source Type: research

An Investigation of Sodium Fusidate and Recombinant Cytochrome P450 Enzymes Inhibition In-Vitro
Conclusion: These findings suggest that there is a potential for sodium fusidate to cause drug interactions when used with other agents that are substrates for rCYP1A2, rCYP2C9, rCYP2C19, rCYP2D6 or rCYP3A4. Understanding the basis of this potential drug interaction will assist in safer use of sodium fusidate in clinical practice. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - October 1, 2016 Category: Drugs & Pharmacology Source Type: research

Application of a “Fit for Purpose” PBPK Model to Investigate the CYP3A4 Induction Potential of Enzalutamide
Conclusion: A “fit for purpose” PBPK model of enzalutamide was successfully developed using public information that recapitulated it’s observed pharmacokinetics, CYP3A4 induction potential and the potential need for dose-adjustment of co-administered CYP3A substrates. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - October 1, 2016 Category: Drugs & Pharmacology Source Type: research

Intracellular Retention of Three Quinuclidine Derivatives in Caco-2 Permeation Experiments: Mechanisms and Impact on Estimating Permeability and Active Efflux Ratio
Conclusion: Our work reveals the different mechanisms involved in cellular retention of these quinuclidine derivatives, and more importantly, demonstrates the value of kinetic analyses with mathematical modeling in minimizing the bias in Papp estimation when assumptions for conventional calculations are violated. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - October 1, 2016 Category: Drugs & Pharmacology Source Type: research

New Screening Criteria Setting on Evaluation of Cytochrome P450 Induction Using HepaRG Cells with Multiplex Branched DNA Technologies in Early Drug Discovery
Conclusion: Our developed assay system, as well as the R10 value, is useful for evaluating the CYP induction potency of NCE in early drug discovery. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - September 30, 2016 Category: Drugs & Pharmacology Source Type: research

Meet Our Editorial Board Member:
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - September 30, 2016 Category: Drugs & Pharmacology Source Type: research

The Uremic Toxin Indoxyl-3-Sulfate Induces CYP1A2 In Primary Human Hepatocytes
Conclusion: These results suggest that the uremic toxin, 3-INDS, is a potent CYP1A2 inducer and lends valuable mechanistic basis for how kidney disease can affect hepatic metabolism. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - September 29, 2016 Category: Drugs & Pharmacology Source Type: research

Formation of A Novel Purine Metabolite through CYP3A4 Bioactivation and Glutathione Conjugation
Conclusion: S-glutathionylation at C-6 position of a purine was proven unequivocally. This previously unreported mechanism constitutes a novel biotransformation for purines. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - June 14, 2016 Category: Drugs & Pharmacology Source Type: research

Elucidating the Mechanism of Tofacitinib Oxidative Decyanation
Conclusion: The proposed mechanism involved the initial oxidation by P450 at the α-carbon to the nitrile group generating an unstable cyanohydrin intermediate; followed by the loss of the nitrile group to form a new geminal diol metabolite (MX). (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - June 14, 2016 Category: Drugs & Pharmacology Source Type: research

In Vitro CYP2D Inhibitory Effect and Influence on Pharmacokinetics and Pharmacodynamic Parameters of Metoprolol Succinate by Terminalia arjuna in Rats
Background: Terminalia arjuna Wight & Arn. (Combretaceae) is a tree having an extensive medicinal potential in cardiovascular disorders. T. arjuna bark extract has been reported to play a significant role as a cardiac stimulant for its beneficial effects in angina. Herb - drug interactions (HDI) are one of the most important clinical concerns in the concomitant consumption of herbs and prescription drugs. Our study was to investigate the in vitro CYP2D inhibition potential of Terminalia arjuna (T. arjuna) extracts in rat liver microsomes and to study the influence of aqueous bark extract of T. arjuna on the oral pharma...
Source: Drug Metabolism Letters - June 14, 2016 Category: Drugs & Pharmacology Source Type: research

Biotransformation of Cobicistat: Metabolic Pathways and Enzymes
Conclusion: This study provided a full map of COBI metabolism. These results can be used to manage CYP-mediated drug-drug interactions and adverse drug reactions that are associated with COBI-containing regimens in human. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - June 14, 2016 Category: Drugs & Pharmacology Source Type: research

In Vitro Study of UGT Metabolism and Permeability of Orientin and Isoorientin, Two Active flavonoid C-glycosides
C-glycosides are important flavonoids with significant pharmacological activities implicated in anticancer and antioxidative effects. However, their characteristics of metabolism and transportation have been rarely investigated. This research aimed to examine the metabolic characteristics of two active C-glycosides, namely, orientin and isoorientin, in human liver microsomes (HLMs) and rat liver microsomes (RLMs) and to confirm the specific uridine 5′-diphospho glucuronosyltransferase (UGT) isoforms involved in glucuronidation by HLMs. Furthermore, the permeability of orientin and isoorientin was also determined by u...
Source: Drug Metabolism Letters - June 14, 2016 Category: Drugs & Pharmacology Source Type: research

Rate-Determining and Rate-Limiting Steps in the Clearance and Excretion of a Potent and Selective p21-Activated Kinase Inhibitor: A Case Study of Rapid Hepatic Uptake and Slow Elimination in Rat
Conclusion: Because the clearance of GNE1 is mediated through uptake transporters rather than metabolism, the extrahepatic expression of Oct1 in kidney and intestine in rat likely plays an important role in the IVIV disconnect in hepatic clearance prediction. The slow process of intestinal secretion is the rate-limiting step for in vivo clearance of GNE1. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - June 14, 2016 Category: Drugs & Pharmacology Source Type: research

Efficiency in Drug Discovery: Liver S9 Fraction Assay As a Screen for Metabolic Stability
Conclusion: In our opinion, replacing liver microsome and hepatocyte assays with S9 assay for high throughput metabolic screening purposes provides the combined benefit of comprehensive and high quality data at a reasonable expense for drug discovery programs. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - June 14, 2016 Category: Drugs & Pharmacology Source Type: research