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 cata...
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 cata...
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

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

Meet Our Editorial Board Member
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - June 30, 2020 Category: Drugs & Pharmacology Source Type: research

Acknowledgements to reviewers
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - January 15, 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 - January 15, 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 - January 15, 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 - January 15, 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 - January 15, 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 - January 15, 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 - January 15, 2020 Category: Drugs & Pharmacology Source Type: research

Meet Our Editorial Board Member
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - January 15, 2020 Category: Drugs & Pharmacology Source Type: research

Formation of a Toxic Quinoneimine Metabolite from Diclofenac: A Quantum Chemical Study
Conclusion: The results demonstrate the possibility of formation of quinoneimine metabolite due to various factors that are involved in the metabolism of diclofenac. The present study may provide the structural in-sights during the drug development processes to avoid the metabolism directed idiosyncratic toxicity. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 30, 2019 Category: Drugs & Pharmacology Source Type: research

Comparison of Rat and Human Pulmonary Metabolism Using Precision-cut Lung Slices (PCLS)
Conclusion: PCLS is a promising tool for the investigation of pulmonary drug metabolism. The data indicates that pulmonary CYP activity is relatively low and that there are significant differences in enzyme activity between rat and human lung. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 30, 2019 Category: Drugs & Pharmacology Source Type: research

“Branched Tail” Oxyquinoline Inhibitors of HIF Prolyl Hydroxylase: Early Evaluation of Toxicity and Metabolism Using Liver-on-a-chip
Conclusion: The optimized adaptaquin analogs are suitable for further preclinical trials. Activation of CYP2B6 with adaptaquin and its variants points to a potential increase in Tylenol toxicity if administered together. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 30, 2019 Category: Drugs & Pharmacology Source Type: research

Unequal Absorption of Radiolabeled and Nonradiolabeled Drug from the Oral Dose Leads to Incorrect Estimates of Drug Absorption and Circulating Metabolites in a Mass Balance Study
Conclusion: Assuming that the radiotracer was proportional to total drug throughout a radiolabeled study was not valid in a 14C study in beagle dogs. This presumably resulted from unequal absorption of the radiotracer and nonradiolabeled test articles from the oral dose due to inequivalent solid forms. We were able to provide a more accurate description of the AME of GDC-0276 in dogs by characterizing the differential absorption of the radiotracer. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 30, 2019 Category: Drugs & Pharmacology Source Type: research

Transport of Bupropion and its Metabolites by the Model CHO and HEK293 Cell Lines
Conclusion: BUP and metabolites are not substrates of the major hepatic transporters tested and thus these hepatic transporters likely do not play a role in the overall disposition of the drug. Our results also suggest that caution should be taken when using the model CHO and HEK293 cell lines to evaluate potential roles of transporters in drug disposition. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 30, 2019 Category: Drugs & Pharmacology Source Type: research

Effect of Aqueous Extract of Azadirachta indica Leaves on Pharmacokineics and Pharmacodynamics of Glipizide
Conclusion: This indicated that the pharmacokinetics and pharmacodynamics of GZ altered by AZI might be due to the induction of CYP3A activity. In conclusion, AZI can decrease the bioavailability of GZ, and hence, it should be cautiously used. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 30, 2019 Category: Drugs & Pharmacology Source Type: research

Use of Cocktail Probe Drugs for Indexing Cytochrome P450 Enzymes in Clinical Pharmacology Studies – Review of Case Studies
Conclusion: The review provides a comprehensive list of various types of cocktail approaches and discusses some key considerations including the evolution of the cocktail approaches over time, perspectives and futuristic views for the use of probe drugs to aid the execution of clinical pharmacology studies and data interpretation. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 30, 2019 Category: Drugs & Pharmacology Source Type: research

Preface
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 30, 2019 Category: Drugs & Pharmacology Source Type: research

Meet Our Editorial Board Member
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - April 30, 2019 Category: Drugs & Pharmacology Source Type: research

Alam K et al. (2018) Drug Metabolism Letters; 12, 24-32.
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 23, 2018 Category: Drugs & Pharmacology Source Type: research

Quantitative Proteomics Reveals Changes in Transporter Protein Abundance in Liver, Kidney and Brain of Mice by Pregnancy
Conclusion: Protein abundance of drug transporters can be significantly changed particularly in the liver by pregnancy. These results will be helpful to understand pregnancy-induced changes in drug/xenobiotic disposition in the mouse model. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 23, 2018 Category: Drugs & Pharmacology Source Type: research

Genistein Affects Expression of Cytochrome P450 (CYP450) Genes in Hepatocellular Carcinoma (HEPG2/C3A) Cell Line
Conclusion: Our results suggest that treatment with genistein in non-toxic concentrations may impact the expression level of CYPs involved in the biotransformation of xenobiotics and drug metabolizing enzymes. Moreover, the downregulation of ATRA metabolism-related genes opens a new research path for the study of genistein as retinoic acid metabolism blocking agent for treating cancer and other pathologies. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 23, 2018 Category: Drugs & Pharmacology Source Type: research

A Novel In vitro Experimental System for the Evaluation of Enteric Drug Metabolism: Cofactor-Supplemented Permeabilized Cryopreserved Human Enterocytes (MetMax™ Cryopreserved Human Enterocytes)
Conclusion: Our results suggest that the MMHE system represents a convenient and robust in vitro experimental system for the evaluation of enteric drug metabolism. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 23, 2018 Category: Drugs & Pharmacology Source Type: research

Hepatic Flavin-containing Monooxygenase and Aldehyde Oxidase Activities in Male Domestic Pigs at Different Ages
Conclusion: Age impact on hepatic activities of both FMO and AO is obvious in domestic male pigs although age patterns of both enzymes are different. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 23, 2018 Category: Drugs & Pharmacology Source Type: research

Effects of Tobacco Nicotine-Derived Nitrosamine Ketone (NNK) Exposures on Brain Alcohol Metabolizing Enzyme Activities
Conclusion: Dual exposures to ethanol and NNK increase brain ethanol metabolism and inhibit the expression of CYP450s that regulate xenobiotic metabolism. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 23, 2018 Category: Drugs & Pharmacology Source Type: research

Acknowledgements to Reviewers
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 22, 2018 Category: Drugs & Pharmacology Source Type: research

In Vitro Drug-Drug Interaction Potential of Sulfoxide and/or Sulfone Metabolites of Albendazole, Triclabendazole , Aldicarb, Methiocarb, Montelukast and Ziprasidone
Conclusion: Based on the findings, a proper risk assessment strategy needs to be factored (i.e., perpetrator and/or victim drug) to overcome any imminent risk of potential clinical drug-drug interaction when sulfoxide/sulfone metabolite(s) generating drugs are coadministered in therapy. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 22, 2018 Category: Drugs & Pharmacology Source Type: research

Using LC Retention Times in Organic Structure Determination: Drug Metabolite Identification
Conclusion: In our experience, this simple methodology allows complementing the discovery efforts that saves resources for in-depth characterization using NMR. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - November 22, 2018 Category: Drugs & Pharmacology Source Type: research

New Perspectives on Acyl Glucuronide Risk Assessment in Drug Discovery: Investigation of In vitro Stability, In situ Reactivity, and Bioactivation
Conclusion: While the compounds tested from “withdrawn” and “warning category” all formed the glutathione adduct in buffer, none from “safe” category formed the glutathione adduct. In contrast, none of the compounds tested from any category formed methoxylamine conjugate, a reaction with putative aldehyde moiety formed via acyl migration. These results, highly favor the nucleophilic displacement as a cause of the reactivity rather than the acyl migration via aldehyde formation. The workflow presented could also be applied in the discovery setting to triage new chemical entities of intere...
Source: Drug Metabolism Letters - November 22, 2018 Category: Drugs & Pharmacology Source Type: research