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.

Mechanistic in vitro studies indicate that the clinical drug –drug interactions between protease inhibitors and rosuvastatin are driven by inhibition of intestinal BCRP and hepatic OATP1B1 with minimal contribution from OATP1B3, NTCP and OAT3
This work sought to clarify the mechanisms underlying clinical DDIs between rosuvastatin and protease inhibitors. Investigating in vitro inhibition of the critical transporter disposition pathways of rosuvastatin, and subsequent incorporation of cell test system derived determined Ki values into mechanistic static equations, enabled successful quantitative prediction of clinical AUCRs. Predictions suggest the mechanisms driving DDI are principally inhibition of intestinal BCRP and hepatic OATP1B1, with minimal contribution from OATP1B3, NTCP or OAT3. AbstractPrevious use of a mechanistic static model to accurately quantify...
Source: Pharmacology Research and Perspectives - February 22, 2023 Category: Drugs & Pharmacology Authors: Robert Elsby, Hannah Coghlan, Jacob Edgerton, David Hodgson, Samuel Outteridge, Hayley Atkinson Tags: ORIGINAL ARTICLE Source Type: research

Defined daily doses in pediatric dosing ‐ a theoretical example
Calculated daily doses from the Summary of product characteristics (SmPC) for paracetamol to children by age group and sex. The bars represent the dose for average weight and the whiskers +/ − 2 standard deviations from the average weight. AbstractA defined daily dose for children (cDDD) taking body weight into account, was proposed as a better measure of drug utilization in children than the World Health Organization's DDD. There is no global definition of DDDs for children, and it is unclear which standard doses should be used for children when conducting drug utilization studies. We used doses according to the authori...
Source: Pharmacology Research and Perspectives - February 20, 2023 Category: Drugs & Pharmacology Authors: Elin Dahl én, Jenny Marianne Kindblom, Elin Eyfells Kimland Tags: SHORT REPORT Source Type: research

Issue Information
(Source: Pharmacology Research and Perspectives)
Source: Pharmacology Research and Perspectives - February 19, 2023 Category: Drugs & Pharmacology Tags: ISSUE INFORMATION Source Type: research

Ultra ‐high‐field pharmacological functional MRI of dopamine D1 receptor‐related interventions in anesthetized rats
Dopamine D1 receptor manipulation induced BOLD signal changes in anesthetized rat brain which detected using pharmacological functional MRI. D1-like receptor agonist increased, while the antagonist decreased the BOLD signal intensity in the striatum, thalamus, and cerebellum. Pharmacological functional MRI can be used for assessment of dopamine receptors-related neurophysiological actions in live animals. AbstractThe dopamine D1 receptor (D1R) is associated with schizophrenia, Parkinson's disease, and attention deficit hyperactivity disorder. Although the receptor is considered a therapeutic target for these diseases, its ...
Source: Pharmacology Research and Perspectives - February 19, 2023 Category: Drugs & Pharmacology Authors: Yuka Kimura, Shunsuke Nakazawa, Kantaro Nishigori, Yuki Mori, Junji Ichihara, Yoshichika Yoshioka Tags: ORIGINAL ARTICLE Source Type: research

Testing the nonclinical Comprehensive In Vitro Proarrhythmia Assay (CiPA) paradigm with an established anti ‐seizure medication: Levetiracetam case study
Levetiracetam (LEV) QT-ogram illustrates that no biologically relevant changes (>10% or 10 ms) in QT-related biomarkers occur up to 10- to 30-fold its free therapeutic plasma concentration (FTPC) in core and follow-up CiPA/S7B nonclinical assays, and the good concordance of this nonclinical dataset with clinical data (TQT study). AbstractLevetiracetam (LEV), a well-established anti-seizure medication (ASM), was launched before the original ICH S7B nonclinical guidance assessing QT prolongation potential and the introduction of the Comprehensive In Vitro Proarrhythmia Assay (CiPA) paradigm. No information was available o...
Source: Pharmacology Research and Perspectives - February 14, 2023 Category: Drugs & Pharmacology Authors: Annie Delaunois, Fran çois‐Xavier Mathy, Miranda Cornet, Vitalina Gryshkova, Chloé Korlowski, François Bonfitto, Juliane Koch, Anne‐Françoise Schlit, Simon Hebeisen, Elisa Passini, Blanca Rodriguez, Jean‐Pierre Valentin Tags: ORIGINAL ARTICLE Source Type: research

Safety, tolerability, and pharmacokinetics of single and multiple ascending Oral doses of DA ‐8010 in healthy subjects: First‐in‐human phase I study
This study assessed the safety, tolerability, and pharmacokinetics of single and multiple oral doses of DA-8010, a muscarinic M3 receptor antagonist, in healthy subjects. This was a randomized, double-blind, placebo-controlled, ascending single (Part A: 1, 2.5, 5, 20, and 40 mg QD fasted and 10 mg QD fasted and fed) and multiple doses (Part B: 5, 10, and 20 mg QD from Days 1 to 7 fasted), sequential-group study. Safety data were analyzed descriptively, time to maximum plasma concentration (tmax) nonparametrically, and pharmacokinetic parameters using power and mixed models and ANOVA. Of 109 subjects randomized (Part ...
Source: Pharmacology Research and Perspectives - February 4, 2023 Category: Drugs & Pharmacology Authors: Dae Young Lee, Min Jung Lee, Chaelim Ryu, Heewon Lee, Ashley Brooks Tags: ORIGINAL ARTICLE Source Type: research

Fatty acids negatively regulate platelet function through formation of noncanonical 15 ‐lipoxygenase‐derived eicosanoids
This study seeks to elucidate whether 15-LOX is required for the formation of 15-oxylipins in the platelet and determine their mechanistic effects on platelet reactivity. In this study, 15-HETrE, 15-HETE, and 15-HEPE attenuated collagen-induced platelet aggregation, and 15-HETrE inhibited platelet aggregation induced by different agonists. The observed anti-aggregatory effect was due to the inhibition of intracellular signaling including αIIbβ3 and protein kinase C activities, calcium mobilization, and granule secretion. While 15-HETrE inhibited platelets partially through activation of peroxisome proliferator-activated ...
Source: Pharmacology Research and Perspectives - January 28, 2023 Category: Drugs & Pharmacology Authors: Adriana Yamaguchi, Christopher Hoorebeke, Benjamin E. Tourdot, Steven C. Perry, Grace Lee, Nicole Rhoads, Andrew Rickenberg, Abigail R. Green, James Sorrentino, Jennifer Yeung, J. Cody Freedman, Theodore R. Holman, Michael Holinstat Tags: ORIGINAL ARTICLE Source Type: research

Pharmacology Research & Perspectives: A Decade of Progress
(Source: Pharmacology Research and Perspectives)
Source: Pharmacology Research and Perspectives - January 24, 2023 Category: Drugs & Pharmacology Authors: Michael F. Jarvis, Emily Davies, Jennifer H. Martin Tags: EDITORIAL Source Type: research