An Effective QWBA/UHPLC-MS/Tissue Punch Approach: Solving a Pharmacokinetic Issue via Quantitative Met-ID
Conclusion: This work illustrates that maximizing the sensitivity of tissue punch radioanalysis and the combination with UHPLC-MS leads to a better insight into pharmacokinetic processes by providing quantitative data with high molecular selectivity. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 22, 2021 Category: Drugs & Pharmacology Source Type: research

Assessment of Prescribability and Switchability by Using Multiple Bioequivalence Assessment Approaches
Conclusion: A single dose of MTX test met the ABE criteria of 80.00% -125.00% for Cmax, AUCo- t, and AUC0-∞, against MTX reference. The study outcome by PBE and IBE approaches proved that MTX Test was bio-inequivalent to MTX reference. Using multiple BE assessment methods in a single BE study is a novel approach and may overcome shortcomings of conventional bioequivalence assessment methods. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 22, 2021 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics Parameters of Diagoxin among Saudi Patients in Qassim Region, Saudi Arabia
Conclusion: In order to individualize the digoxin dosage regimens, this model can be used to predict digoxin serum concentration. Further studies are needed to clarify the effects of nutritional status and co-administration of medications on digoxin pharmacokinetics. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 22, 2021 Category: Drugs & Pharmacology Source Type: research

The Role of Aldehyde Oxidase in the Metabolic Clearance of Substituted Benzothiazoles
Conclusion: To our knowledge, such an observation of in vitro and in vivo oxidation of substituted benzothiazole by AO has not been reported before. The results helped the medicinal chemists design compounds that avoid AO-mediated metabolism and with better ADME property. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 22, 2021 Category: Drugs & Pharmacology Source Type: research

Biological Importance, Therapeutic Benefit and Analytical Aspects of Bioactive Flavonoid Pectolinarin in the Nature
Conclusion: Scientific data of the present work signified the biological potential and therapeutic benefit of pectolinarin. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 22, 2021 Category: Drugs & Pharmacology Source Type: research

Management of Acute Aluminum Phosphide Poisoning: Has Anything Changed?
Due to its easy availability, rapid and severe toxicity, and no specific antidote, aluminum phosphide has emerged as a lethal toxin, commonly used for suicidal intent in agricultural communities. Despite various advances in medicine, this compound’s toxicity is poorly understood, and it still has a very high case fatality rate with no definitive treatment options available. This review aims to understand the mechanism of toxicity, clinical toxidrome of acute aluminum phosphide poisoning, and the available therapeutic options, including recent advances. A literature review was performed searching PubMed, EMBASE Ovid, and ...
Source: Drug Metabolism Letters - November 22, 2021 Category: Drugs & Pharmacology Source Type: research

The Link Between Conventional and Novel Anti-Cancer Therapeutics with Thrombotic Microangiopathy
Conclusion: As novel cancer therapies are developed, it is paramount to pursue a better understanding of conventional and novel chemotherapeutic agents and their role in kidney disease. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 22, 2021 Category: Drugs & Pharmacology Source Type: research

Meet the Editorial Board Member
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 22, 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 - May 5, 2021 Category: Drugs & Pharmacology Source Type: research

Hemodynamic Assessment and In vivo Catabolism of Adenosine 5’-triphosphate in Doxorubicin or Isoproterenol-induced Cardiovascular Toxicity
Objective: Previous studies have shown that catabolism of adenosine 5’-triphosphate (ATP) in systemic blood is a potential surrogate biomarker for cardiovascular toxicity. We compared the acute toxicity of high doses of doxorubicin (DOX) and isoproterenol (ISO) on hemodynamics and ATP catabolism in the systemic circulation. Methods: sprague Dawley (SD) rats (n = 8 - 11) were each given either a single dose of 30 mg/kg ISO, or a twice-daily dose of 10 mg/kg of DOX or 4 doses of normal saline (control) by subcutaneous injection. Blood samples were collected up to 6 hours for measuring concentrations of ATP and its cataboli...
Source: Drug Metabolism Letters - May 4, 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 - May 4, 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 - May 4, 2021 Category: Drugs & Pharmacology Source Type: research

The Effect of Pomegranate Juice on the Expression of Some Murine UDP-Glucuronosyltransferases Genes
Conclusion: Some ugt mRNA levels may be reduced by the ingestion of pomegranate juice, which may reduce the metabolism of their drug substrates. The consequences may be an accumulation of such drugs in the body and enhanced toxicity. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Hemodynamic Assessment and in vivo Catabolism of Adenosine 5’-triphosphate in Doxorubicin or Isoproterenol-induced Cardiovascular Toxicity
Objective: Previous studies have shown that catabolism of adenosine 5’-triphosphate (ATP) in systemic blood is a potential surrogate biomarker for cardiovascular toxicity. We compared the acute toxicity of high doses of doxorubicin (DOX) and isoproterenol (ISO) on hemodynamics and ATP catabolism in the systemic circulation. Methods: sprague Dawley (SD) rats (n = 8 - 11) were each given either a single dose of 30 mg/kg ISO, or a twice-daily dose of 10 mg/kg of DOX or 4 doses of normal saline (control) by subcutaneous injection. Blood samples were collected up to 6 hours for measuring concentrations of ATP and its cataboli...
Source: Drug Metabolism Letters - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

Amorphous Solid Dispersion Based Oral Disintegrating Film of Ezetimibe: Development and Evaluation
Conclusion: The study revealed that the formulation approach could overcome the biopharmaceutical challenge of solubility as well as low bioavailability issues of ezetimibe. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 15, 2021 Category: Drugs & Pharmacology Source Type: research