Pharmacokinetics of Darolutamide in Mouse - Assessment of the Disposition of the Diastereomers, Key Active Metabolite and Interconversion Phenomenon: Implications to Cancer Patients
Conclusion: In lieu of the human pharmacokinetic data, although the administration of diastereomeric darolutamide was justified, it is proposed to delineate the clinical pharmacokinetics of S,Rdarolutamide and S,S-darolutamide relative to darolutamide in future clinical pharmacology studies. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 15, 2021 Category: Drugs & Pharmacology Source Type: research
Carbon-Carbon Bond Cleavage Catalyzed by Human Cytochrome P450 Enzymes: α-Ketol as the Key Intermediate Metabolite in Sequential Metabolism of Olanexidine
Conclusion: 3,2-ketol olanexidine and 2,3-ketol olanexidine were confirmed as the key intermediates in carbon-carbon bond cleavage. Its mechanism is proposed that a nucleophilic addition of iron-peroxo species, generated by CYP2D6 and CYP3A4/5, to the carbonyl group caused the carbon-carbon bond cleavage between the adjacent hydroxyl and ketone groups. As results, 2,3-ketol olanexidine formed a C6 side chain acid metabolite. While, 3,2-ketol olanexidine formed a C6 side chain aldehyde intermediate, which was either oxidized to a C6 side chain acid metabolite or reduced to a C6 side chain hydroxyl metabolite. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 15, 2021 Category: Drugs & Pharmacology Source Type: research
Recent Progress in Prediction Systems for Drug-induced Liver Injury Using In Vitro Cell Culture
Conclusion: Different co-culture systems consisting of human hepatocyte-derived cells and other immune/inflammatory cells have enabled the identification of DILI-causing drugs and of the actual mechanisms of action. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 15, 2021 Category: Drugs & Pharmacology Source Type: research
Major CYP450 polymorphism Among Saudi Patients
Conclusion: The current evidence suggests that Saudi resembled European in the frequency of CYP2C19, Caucasians in both the incidence of CYP2C9 and CYP2C19m1, and the absence of CYP2C19m2. The CYP2D6*41 allele frequency in Saudi is relatively high. We recommend further research to evaluate the basic and clinical relevance of gene polymorphism in such ethnicity. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 15, 2021 Category: Drugs & Pharmacology Source Type: research
Pharmacokinetics of Darolutamide, its Diastereomers and Active Metabolite in the Mouse: Response to Saini NK et al. (2020)
Conclusion: The darolutamide diastereomer ratio changes upon administration in mice and other species due to interconversion through keto-darolutamide. This is not considered clinically relevant since both diastereomers and keto- darolutamide are pharmacologically similar in vitro. Based on the high protein binding of keto-darolutamide, its contribution in vivo in humans is considered low. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 15, 2021 Category: Drugs & Pharmacology Source Type: research
Assessment of Herb-Drug Interactions Based on the Pharmacokinetic Changes of Probe Drug, Midazolam
Conclusion: Probe drug technique is one of the easiest ways for predicting CYP enzyme-mediated herb-drug interactions. Midazolam shows a good response in clinical studies because of short halflife and low harmfulness compared with other probe drugs. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 15, 2021 Category: Drugs & Pharmacology Source Type: research
A Short Exploration of Selected Sensitive CYP3A4 Substrates (Probe Drug)
Conclusion: It is concluded that midazolam shows a good response in all clinical studies because of its lesser half-life and bioavailability when compared with other probe drugs. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 15, 2021 Category: Drugs & Pharmacology Source Type: research
Preface
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 15, 2021 Category: Drugs & Pharmacology Source Type: research
Acknowledgements to reviewers
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - June 30, 2020 Category: Drugs & Pharmacology Source Type: research
Oral Bioavailability Enhancement of Amisulpride: Complexation and its Pharmacokinetics and Pharmacodynamics Evaluations
Conclusion: Pharmacodynamic studies in mice showed improved effectiveness of drug compared to pure drug. The oral bioavailability of AMS was improved from 48% to 78%. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - June 30, 2020 Category: Drugs & Pharmacology Source Type: research
Assessment of Inhibition of Bovine Hepatic Cytochrome P450 by 43 Commercial Bovine Medicines Using a Combination of In Vitro Assays and Pharmacokinetic Data from the Literature
Conclusion: This combination of in vitro assay and in vivo Cmax data provides a good approach to assess the inhibition of bovine medicines on bovine hepatic CYP450. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - June 30, 2020 Category: Drugs & Pharmacology Source Type: research
The Effects of Special Patient Population Plasma on Pharmacokinetic Quantifications Using LC-MS/MS
Conclusion: Special population plasma did not affect quantitation of drugs with a wide range of plasma protein binding levels in human plasma. With the confirmation that there is no impact on quantification from the matrix, the bioanalytical method can be used to support the pharmacokinetic evaluations for clinical studies in special populations. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - June 30, 2020 Category: Drugs & Pharmacology Source Type: research
Imatinib Uptake into Cells is Not Mediated by Organic Cation Transporters OCT1, OCT2, or OCT3, But is Influenced by Extracellular pH
Conclusion: Imatinib is not a substrate of OCTs 1-3 while the environmental pH modulates cellular disposition of imatinib. The observation that a slightly acidic extracellular pH influences imatinib cellular accumulation is important, considering the low extracellular pH reported in the hematopoietic leukemia/ cancer cell microenvironment. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - June 30, 2020 Category: Drugs & Pharmacology Source Type: research
Prominence of Oxidative Stress in the Management of Anti-tuberculosis Drugs Related Hepatotoxicity
Advanced medical services and treatments are available for treating Tuberculosis. Related prevalence has increased in recent times. Unfortunately, the continuous consumption of related drugs is also known for inducing hepatotoxicity which is a critical condition and cannot be overlooked. The present review article has focused on the pathways causing these toxicities and also the role of enzyme CYP2E1, hepatic glutathione, Nrf2-ARE signaling pathway, and Membrane Permeability Transition as possible targets which may help in preventing the hepatotoxicity induced by the drugs used in the treatment of tuberculosis. (Source: Dr...
Source: Drug Metabolism Letters - June 30, 2020 Category: Drugs & Pharmacology Source Type: research
A Practical Perspective on the Evaluation of Small Molecule CNS Penetration in Drug Discovery
The separation of the brain from blood by the blood-brain barrier and the bloodcerebrospinal fluid (CSF) barrier poses unique challenges for the discovery and development of drugs targeting the central nervous system (CNS). This review will describe the role of transporters in CNS penetration and examine the relationship between unbound brain (Cu-brain) and unbound plasma (Cu-plasma) or CSF (CCSF) concentration. Published data demonstrate that the relationship between Cu-brain and Cu-plasma or CCSF can be affected by transporter status and passive permeability of a drug and CCSF may not be a reliable surrogate for CNS pene...
Source: Drug Metabolism Letters - June 30, 2020 Category: Drugs & Pharmacology Source Type: research
