Pharmacology Research and Perspectives This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Metabolism of sumatriptan revisited
Proposed metabolic pathway of sumatriptan. AbstractScientific literature describes that sumatriptan is metabolized by oxidative deamination of its dimethylaminoethyl residue by monoamine oxidase A (MAO A) and not by cytochrome P450 (CYP)-mediated demethylation, as is usual for such structural elements. Using recombinant human enzymes and HPLC-MS analysis, we found that CYP enzymes may also be involved in the metabolism of sumatriptan. The CYP1A2, CYP2C19, and CYP2D6 isoforms converted this drug intoN-desmethyl sumatriptan, which was further demethylated toN,N-didesmethyl sumatriptan by CYP1A2 and CYP2D6. Otherwise, sumatri...
Source: Pharmacology Research and Perspectives - January 19, 2023 Category: Drugs & Pharmacology Authors: Timo P östges, Matthias Lehr Tags: ORIGINAL ARTICLE Source Type: research

Comparative evaluation of biased agonists Sarcosine1, d ‐Alanine8‐Angiotensin (Ang) II (SD Ang II) and Sarcosine1, Isoleucine8‐Ang II (SI Ang II) and their radioiodinated congeners binding to rat liver membrane AT1 receptors
Overview of outcomes resulting from action of full AT1R agonists versus biased AT1R agonists. AbstractAngiotensin II analogue and β-arrestin biased agonist TRV027 (Sarcosine1,d-Alanine8-Angiotensin (Ang) II; SD Ang II), developed by Trevena, Inc. in the early 2010s, brought hopes of a novel treatment for cardiovascular diseases, due to its ability to simultaneously cause signaling through the β-arrestin signaling pathway, while antagonizing the pathophysiological effects of Ang II mediated by the AT1 receptor G protein signaling cascades. However, a phase II clinical trial of this agent revealed no significant benefit co...
Source: Pharmacology Research and Perspectives - January 14, 2023 Category: Drugs & Pharmacology Authors: Natalia M. Noto, Yazmin M. Restrepo, Hong W. Pang, Filipe Stoyell ‐Conti, Crystal A. West, Robert C. Speth Tags: ORIGINAL ARTICLE Source Type: research

Vinblastine pharmacokinetics in mouse, dog, and human in the context of a physiologically based model incorporating tissue ‐specific drug binding, transport, and metabolism
Schematic of Vinblastine PBPK Model. AbstractVinblastine (VBL) is a vinca alkaloid-class cytotoxic chemotherapeutic that causes microtubule disruption and is typically used to treat hematologic malignancies. VBL is characterized by a narrow therapeutic index, with key dose-limiting toxicities being myelosuppression and neurotoxicity. Pharmacokinetics (PK) of VBL is primarily driven by ABCB1-mediated efflux and CYP3A4 metabolism, creating potential for drug –drug interaction. To characterize sources of variability in VBL PK, we developed a physiologically based pharmacokinetic (PBPK) model in Mdr1a/b(−/−) knockout and...
Source: Pharmacology Research and Perspectives - January 12, 2023 Category: Drugs & Pharmacology Authors: Sandra Witta, Keagan P. Collins, Dominique A. Ramirez, Joshua D. Mannheimer, Luke A. Wittenburg, Daniel L. Gustafson Tags: ORIGINAL ARTICLE Source Type: research

A humanized anti ‐cocaine mAb antagonizes the cardiovascular effects of cocaine in rats
An increase in ejection fraction was seen after the cocaine push with the maximum change occurring at 25  min. Treatment with h2E2 1 h before the cocaine push did not have any effect on cardiac parameters. Subsequent cocaine treatment had no effect on the ejection fraction, indicating that the antibody-bound cocaine does not affect the heart. Cocaine in the presence of h2E2 is pharmacologically inert and h2E2 may have additional clinical utility for reversing cocaine effects on the cardiovascular system. AbstractThe recombinant monoclonal anti-cocaine antibody, h2E2, sequesters cocaine in plasma increasing concentrations...
Source: Pharmacology Research and Perspectives - January 12, 2023 Category: Drugs & Pharmacology Authors: Sheryl E. Koch, Jordan A. Marckel, Jack Rubinstein, Andrew B. Norman Tags: ORIGINAL ARTICLE Source Type: research

Comparison of creatinine ‐based equations for estimating renal function for digoxin dose adjustment in patients with atrial fibrillation and heart failure
The estimated glomerular filtration rate by the Modification of Diet in Renal Disease (eGFRMDRD) equation deindexed based on body surface area had the highest correlation with digoxin trough concentrations (r = −0.450) compared to the Cockcroft-Gault (r = −0.415) or deindexed eGFR based on the Chronic Kidney Disease Epidemiology Collaboration (eGFRCKD-EPI) equation (r = −0.416). AbstractThe aim of this study was to determine an appropriate equation for estimating renal function to dose regulate the serum digoxin trough concentration to a target of<0.9  ng/ml in patients with atrial fibrillation (AF) and ...
Source: Pharmacology Research and Perspectives - January 11, 2023 Category: Drugs & Pharmacology Authors: Masahiro Sakai, Toshinori Hirai, Satoshi Shitara, Takuya Iwamoto, Tsuyoshi Shiga Tags: SHORT REPORT Source Type: research

A humanized anti ‐cocaine mAb antagonizes the cardiovascular effects of cocaine in rats
An increase in ejection fraction was seen after the cocaine push with the maximum change occurring at 25  min. Treatment with h2E2 1 h before the cocaine push did not have any effect on cardiac parameters. Subsequent cocaine treatment had no effect on the ejection fraction, indicating that the antibody-bound cocaine does not affect the heart. Cocaine in the presence of h2E2 is pharmacologically inert and h2E2 may have additional clinical utility for reversing cocaine effects on the cardiovascular system. AbstractThe recombinant monoclonal anti-cocaine antibody, h2E2, sequesters cocaine in plasma increasing concentrations...
Source: Pharmacology Research and Perspectives - January 11, 2023 Category: Drugs & Pharmacology Authors: Sheryl E. Koch, Jordan A. Marckel, Jack Rubinstein, Andrew B. Norman Tags: ORIGINAL ARTICLE Source Type: research

Vinblastine pharmacokinetics in mouse, dog, and human in the context of a physiologically based model incorporating tissue ‐specific drug binding, transport, and metabolism
Schematic of Vinblastine PBPK Model. AbstractVinblastine (VBL) is a vinca alkaloid-class cytotoxic chemotherapeutic that causes microtubule disruption and is typically used to treat hematologic malignancies. VBL is characterized by a narrow therapeutic index, with key dose-limiting toxicities being myelosuppression and neurotoxicity. Pharmacokinetics (PK) of VBL is primarily driven by ABCB1-mediated efflux and CYP3A4 metabolism, creating potential for drug –drug interaction. To characterize sources of variability in VBL PK, we developed a physiologically based pharmacokinetic (PBPK) model in Mdr1a/b(−/−) knockout and...
Source: Pharmacology Research and Perspectives - January 11, 2023 Category: Drugs & Pharmacology Authors: Sandra Witta, Keagan P. Collins, Dominique A. Ramirez, Joshua D. Mannheimer, Luke A. Wittenburg, Daniel L. Gustafson Tags: ORIGINAL ARTICLE Source Type: research

Comparison of creatinine ‐based equations for estimating renal function for digoxin dose adjustment in patients with atrial fibrillation and heart failure
The estimated glomerular filtration rate by the Modification of Diet in Renal Disease (eGFRMDRD) equation deindexed based on body surface area had the highest correlation with digoxin trough concentrations (r = −0.450) compared to the Cockcroft-Gault (r = −0.415) or deindexed eGFR based on the Chronic Kidney Disease Epidemiology Collaboration (eGFRCKD-EPI) equation (r = −0.416). AbstractThe aim of this study was to determine an appropriate equation for estimating renal function to dose regulate the serum digoxin trough concentration to a target of<0.9  ng/ml in patients with atrial fibrillation (AF) and ...
Source: Pharmacology Research and Perspectives - January 10, 2023 Category: Drugs & Pharmacology Authors: Masahiro Sakai, Toshinori Hirai, Satoshi Shitara, Takuya Iwamoto, Tsuyoshi Shiga Tags: SHORT REPORT Source Type: research

Impact of solute carrier transporter gene polymorphisms on serum creatinine concentrations in healthy volunteers
In this study, muscle mass, serum cystatin C concentration, body fat percentage, serum albumin concentration, and MATE2-K gene polymorphism were independent factors affecting serum creatinine concentration. TheSLC47A2 c.-130G  >  A polymorphism may affect creatinine dynamics in the proximal tubules. AbstractIn this study, we investigated the impact of single nucleotide polymorphisms in solute carrier (SLC) transporters, that is,SLC22A7 c.1586  + 206A >  G,SLC22A2 c.808G  >  T,SLC22A3 c.1233G  >  A,SLC47A1 c.922-158G  >  A, andSLC47A2 c.-130G  >  A, on serum creatinine (SCr) con...
Source: Pharmacology Research and Perspectives - January 6, 2023 Category: Drugs & Pharmacology Authors: Satoshi Yokoyama, Junichi Nakagawa, Masakiyo Kudo, Naoya Aiuchi, Tatsuya Seito, Mizuri Isida, Tatsuya Mikami, Kazushige Ihara, Shigeyuki Nakaji, Takenori Niioka Tags: INVITED REVIEW Source Type: research

Comparison of the mathematical equation and trapezoidal approach for 24  h area under the plasma concentration‐time curve calculation in patients who received intravenous vancomycin in an acute care setting
Correlation between calculated AUC (mg ·h/L) by Method 1 (trapezoidal method) and Method 2 (equation method); AUC-equation A method (▲), AUC-equation B method (○) classification by pair of serum vancomycin concentrations were brought to determine AUC from equation A and B. (C2: vancomycin concentration at the end of infusion,C2.5: vancomycin concentration at 2.5  h after starting the infusion,C3: vancomycin concentration at 3  h after starting the infusion andCT: vancomycin concentration before the true trough concentration 1  h,R2, the coefficient of determination). AbstractThe current recommendation for therap...
Source: Pharmacology Research and Perspectives - January 2, 2023 Category: Drugs & Pharmacology Authors: Pimonrat Chanapiwat, Taniya Paiboonvong, Pinyo Rattanaumpawan, Preecha Montakantikul Tags: ORIGINAL ARTICLE Source Type: research

Selective somatostatin receptor 5 inhibition improves hepatic insulin sensitivity
In conclusion, selective SSTR5 inhibition can improve insulin sensitivity by enhancing liver insulin action. AbstractDiabetes is a metabolic disorder with an increasing global prevalence. Somatostatin (SST), a peptide hormone, regulates hormone secretion via five SST receptor (SSTR) subtypes (SSTR1 –5) in a tissue-specific manner. As SSTR5 is expressed in pancreatic β-cells and intestinal L-cells, studies have suggested that SSTR5 regulates glucose tolerance through insulin and incretin secretion, thereby having a prominent role in diabetes. Moreover, SSTR5 knockout (KO) mice display enhanc ed insulin sensitivity; howev...
Source: Pharmacology Research and Perspectives - December 31, 2022 Category: Drugs & Pharmacology Authors: Yumiko Okano Tamura, Jun Sugama, Shin ‐ichi Abe, Yuji Shimizu, Hideki Hirose, Masanori Watanabe Tags: ORIGINAL ARTICLE Source Type: research