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
