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.

Modeling time ‐delayed concentration‐QT effects with ACT‐1014‐6470, a novel oral complement factor 5a receptor 1 (C5a1 receptor) antagonist
AbstractThe novel oral complement factor 5a receptor 1 antagonist ACT-1014-6470 was well tolerated in single- and multiple-ascending dose studies, including 24  h Holter electrocardiogram (ECG) recordings evaluating its cardiodynamics based on data from single doses of 30–200 mg and twice-daily (b.i.d.) dosing of 30–120 mg for 4.5 days. By-time point, categorical, and morphological analyses as well as concentration-QT modeling and simulations w ere performed. No relevant effect of ACT-1014-6470 on ECG parameters was observed in the categorical and morphological analyses. After single-dose administration, the by...
Source: Pharmacology Research and Perspectives - July 20, 2023 Category: Drugs & Pharmacology Authors: Marion Anliker ‐Ort, Chih‐hsuan Hsin, Andreas Krause, Marc Pfister, John Anker, Jasper Dingemanse, Priska Kaufmann Tags: ORIGINAL ARTICLE Source Type: research

Investigation of the GnRH antagonist degarelix isomerization in biological matrices
We investigated the degradation of the GnRH antagonist Degarelix in various biologic media by the tailor-made HPLC method, which allows precise determination of 5-Aph(Hyd)-Degarelix isomer, and we discovered a rapid and irreversible conversion of Degarelix API into the corresponding hydantoin isomer in serum, suggesting that it can be a potential drug metabolite in vivo. This finding can improve the understanding of the metabolic pathways of Degarelix. AbstractOne of the main objectives of peptide drug design is the improvement of peptide pharmacokinetics with maintaining biological activity, which can be achieved by the c...
Source: Pharmacology Research and Perspectives - July 17, 2023 Category: Drugs & Pharmacology Authors: Lucia Ferrazzano, Alessandra Tolomelli, Ivan Guryanov, Marco Macis, Ulrich Abel, Antonio Ricci, Walter Cabri Tags: ORIGINAL ARTICLE Source Type: research

Cisplatin cycles treatment sustains cardiovascular and renal damage involving TLR4 and NLRP3 pathways
In conclusion, cisplatin cycles provoke a low grade pro-inflammatory systemic state. Kidney was more sensitive than cardiovascular tissues to this pro-inflammator y state. TLR4 and NLRP3 are key pathways involved in renal tissue damage, NLRP3 is the main pathway involved in cardiac toxicity and TLR4 pathway in resistance vessel toxicity. (Source: Pharmacology Research and Perspectives)
Source: Pharmacology Research and Perspectives - July 10, 2023 Category: Drugs & Pharmacology Authors: Antonio Gonz ález, Soledad García‐Gómez‐Heras, Raquel Franco‐Rodríguez, Visitación López‐Miranda, Esperanza Herradón Tags: ORIGINAL ARTICLE Source Type: research

Impact of metformin on statin ‐associated myopathy risks in dyslipidemia patients
This study found that a comedication with metformin was associated with decreased myopathy risk in statin-treated dyslipidemia patients compared to statin-only users. Our findings suggest that metformin may provide protective effects on potential muscle toxicities induced by statin therapy. (Source: Pharmacology Research and Perspectives)
Source: Pharmacology Research and Perspectives - July 8, 2023 Category: Drugs & Pharmacology Authors: Keunhyeong Bak, Suhyeon Moon, Minjung Ko, Yeo Jin Choi, Sooyoung Shin Tags: ORIGINAL ARTICLE Source Type: research

Application of physiologically based pharmacokinetic modeling to understand real ‐world outcomes in patients receiving imatinib for chronic myeloid leukemia
Combining real word clinical data and pharmacokinetic modeling, this study investigated the exposure-response relationship for imatinib in people with chronic myeloid leukemia. Patients with higher imatinib exposure were more likely to achieve clinical response, but also the risk of imatinib-related harms. AbstractWe aimed to use physiologically based pharmacokinetic (PBPK) modeling and simulation to predict imatinib steady-state plasma exposure in patients with chronic myeloid leukemia (CML) to investigate variability in outcomes. A validated imatinib PBPK model (Simcyp Simulator) was used to predict imatinib AUCss, Css,m...
Source: Pharmacology Research and Perspectives - July 7, 2023 Category: Drugs & Pharmacology Authors: Josephine A. Adattini, Jeffry Adiwidjaja, Annette S. Gross, Andrew J. McLachlan Tags: ORIGINAL ARTICLE Source Type: research

Role of efficacy as a determinant of locomotor activation by mu ‐opioid receptor (MOR) ligands in female and male mice. II. Effects of novel MOR‐selective phenylmorphans with high‐to‐low MOR efficacy
AbstractLow-efficacy mu-opioid receptor (MOR) agonists represent promising therapeutics, but existing compounds (e.g., buprenorphine, nalbuphine) span a limited range of low MOR efficacies and have poor MOR selectivity. Accordingly, new and selective low-efficacy MOR agonists are of interest. A novel set of chiral C9-substituted phenylmorphans has been reported to display improved MOR selectivity and a range of high-to-low MOR efficacies under other conditions; however, a full opioid receptor binding profile for these drugs has not been described. Additionally, studies in mice will be useful for preclinical characterizatio...
Source: Pharmacology Research and Perspectives - July 4, 2023 Category: Drugs & Pharmacology Authors: Edna J. Santos, Nima Nassehi, Eric W. Bow, Dana R. Chambers, Eugene  S. Gutman, Arthur E. Jacobson, Joshua A. Lutz, Samuel A. Marsh, Kenner C. Rice, Agnieszka Sulima, Dana E. Selley, S. Stevens Negus Tags: ORIGINAL ARTICLE Source Type: research

Analysis of safety specifications in risk management plan at the time of drug approval and addition of clinically significant adverse reactions in the package insert post ‐approval in Japan
In this study, we examine the relationship between the safety specifications (SSs) in RMPs at the time of drug approval and the adverse reactions (ARs) added to the clinically significant adverse reactions (CSARs) section of the package inserts (PIs) post-approval to determine whether SSs constitute useful drug information for pharmacists. The analysis included new active ingredient-containing drugs approved in Japan from FY2013 to 2019. A 2  × 2 contingency table was created and analyzed using odds ratios (ORs) and Fisher's exact test. The OR was 14.22 (95% CI: 7.85–24.77;p <  .001), which indicates a strong...
Source: Pharmacology Research and Perspectives - June 27, 2023 Category: Drugs & Pharmacology Authors: Rieko Saito, Seiko Miyazaki Tags: ORIGINAL ARTICLE Source Type: research