Pharmacokinetics, mass balance, tissue distribution, metabolism, and excretion of praliciguat, a clinical‐stage soluble guanylate cyclase stimulator in rats
| العنوان: | Pharmacokinetics, mass balance, tissue distribution, metabolism, and excretion of praliciguat, a clinical‐stage soluble guanylate cyclase stimulator in rats |
|---|---|
| المؤلفون: | Jenny Tobin, Albert T. Profy, Ali R. Banijamali, Mark G. Currie, James Wakefield, Jaime L. Masferrer, G. Todd Milne, Daniel P. Zimmer, Andrew Carvalho, Peter Germano, Barden Timothy Claude |
| المصدر: | Pharmacology Research & Perspectives Pharmacology Research & Perspectives, Vol 8, Iss 2, Pp n/a-n/a (2020) |
| بيانات النشر: | John Wiley and Sons Inc., 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, sGC, Metabolite, praliciguat, Glucuronidation, Adipose tissue, RM1-950, 030226 pharmacology & pharmacy, Excretion, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, Feces, 0302 clinical medicine, Soluble Guanylyl Cyclase, Pharmacokinetics, Oral administration, nitric oxide, Internal medicine, QWBA, medicine, Animals, Bile, Rats, Long-Evans, Tissue Distribution, General Pharmacology, Toxicology and Pharmaceutics, Original Articles, Bioavailability, cGMP, Endocrinology, Pyrimidines, Neurology, chemistry, 030220 oncology & carcinogenesis, Pyrazoles, Original Article, excretion, Therapeutics. Pharmacology, absorption, metabolism, pharmacokinetics, Drug metabolism, mass balance |
| الوصف: | The pharmacokinetics (PK), metabolism, excretion, mass balance, and tissue distribution of [14C]praliciguat were evaluated following oral administration of a 3‐mg/kg dose in Sprague‐Dawley rats and in a quantitative whole‐body autoradiography (QWBA) study conducted in male Long‐Evans rats. Plasma T max was 1 hour and the t 1/2 of total plasma radioactivity was 23.7 hours. Unchanged praliciguat accounted for 87.4%, and a minor metabolite (N‐dealkylated‐praliciguat) accounted for 7.6% of the total radioactivity in plasma through 48 hours (AUC0‐48). Tissues with the highest exposure ratios relative to plasma were liver, intestines, adrenal gland, and adipose, and those with the lowest values were seminal vesicle, blood, CNS tissues, lens of the eye, and bone. Most of the [14C]praliciguat‐derived radioactivity was excreted within 48 hours after oral administration. Mean cumulative recovery of the administered radioactivity in urine and feces over 168 hours was 3.7% and 95.7%, respectively. Unchanged praliciguat was not quantifiable in urine or bile of cannulated rats; however, based on the total radioactivity in these fluids, a minimum of approximately 82% of the orally administered dose was absorbed. [14C]Praliciguat was metabolized via oxidative and glucuronidation pathways and the most abundant metabolites recovered in bile were praliciguat‐glucuronide and hydroxy‐praliciguat‐glucuronide. These results indicate that praliciguat had rapid absorption, high bioavailability, extensive tissue distribution, and elimination primarily via hepatic metabolism. |
| اللغة: | English |
| تدمد: | 2052-1707 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b0b3e4df24159164c127118e8e21c0b4 http://europepmc.org/articles/PMC7171252 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b0b3e4df24159164c127118e8e21c0b4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20521707 |
|---|