Detail of "313348-27-5"

Reference

The future of pharmacologic stress: selective A2A adenosine receptor agonists

The future of pharmacologic stress: selective A2A adenosine receptor agonists. Cerqueira, Manuel D. (Division of Cardiology, Georgetown University Medical Center, Washington, DC, USA). American Journal of Cardiology, 94(2A), 33D-42D (English) 2004 Excerpta Medica, Inc. CODEN: AJCDAG. ISSN: 0002-9149. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review. Adenosine and dipyridamole, the currently available vasodilators for myocardial perfusion imaging, produce hyperemic coronary flow by stimulating A2A adenosine receptors on arteriolar vascular smooth muscle cells. However, both vasodilators nonselectively activate A1, A2B, and A3 adenosine receptors, which contributes to common undesirable effects. In the development of a novel pharmacol. stress agent, more selective agonism of the A2A receptor subtype would be desirable. Currently, 2 selective A2A adenosine receptor agonists are being evaluated in phase 3 studies as pharmacol. stress agents. The highly selective, potent, low affinity A2A adenosine agonist regadenoson (also known as CVT-3146) holds significant potential as a pharmacol. stress agent, based on available results from exptl. and clin. trials. Regadenoson produces maximal hyperemia quickly and maintains it for an optimal duration that is practical for radionuclide myocardial perfusion imaging. 58-61-7 and 313348-27-5 are just another two chemicals used in this study. Regadenoson's simple rapid bolus administration and short duration of hyperemic effect point to an advantage of enhanced control for the clinician. .

A population pharmacokinetic/pharmacodynamic analysis of regadenoson, an adenosine A2A-receptor agonist, in healthy male volunteers

All Rights Reserved. Some chemicals with cas registry numbers like 313348-27-5 are also used. A population pharmacokinetic/pharmacodynamic analysis of regadenoson, an adenosine A2A-receptor agonist, in healthy male volunteers. Gordi, Toufigh; Frohna, Paul; Sun, Hai-Ling; Wolff, Andrew; Belardinelli, Luiz; Lieu, Hsiao (CV Therapeutics, Inc., Palo Alto, CA, USA). Clinical Pharmacokinetics, 45(12), 1201-1212 (English) 2006 Adis International Ltd. CODEN: CPKNDH. ISSN: 0312-5963. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Objectives: The aims of this study were to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of regadenoson (CVT-3146) in healthy, male volunteers. Methods: Thirty-six healthy, male volunteers aged 18-50 years were included in this randomized, double-blind, crossover, placebo-controlled study to evaluate single i.v. bolus doses of regadenoson that ranged from 0.1 to 30.0 mg/kg. Subjects received one dose of regadenoson or placebo on successive days while supine, then the same dose of regadenoson or placebo on successive days while standing. As part of the safety evaluation, vital signs and adverse events were monitored and recorded throughout the course of the study in all subjects. Up to 20 plasma samples were collected for regadenoson concn. detn. within the 24 h after each supine dosage. All urine was collected during the 24-h time period post-dose and an aliquot was used for the detn. of the regadenoson concn. Heart rate and blood pressure were recorded at many of the same timepoints that the samples for the pharmacokinetic anal. were taken. A non linear mixed-effect modeling approach, using the software NONMEM, was utilized in modeling the plasma and urine concn.-time profiles and temporal changes in heart rate after regadenoson administration in the supine position. The influences of several covariates, including body wt., body mass index and age, on pharmacokinetic model parameters were investigated. Results: Adverse events were more prevalent at regadenoson doses above 3 mg/kg, and the increase in the occurrence of adverse events was dose-related. Most of the adverse events were related to vasodilation and an increase in heart rate and were generally of mild to moderate severity. Based on the severity and frequency of adverse events, the max. tolerated doses of regadenoson were deemed to be 10 mg/kg in the standing position and 20 mg/kg in the supine position. The pharmacokinetics of regadenoson were successfully described by a three-compartment model with linear clearance. Following i.v. bolus dose administration, regadenoson was rapidly distributed throughout the body, followed by relatively slower elimination (terminal elimination half-life of approx. 2 h). The clearance was estd. to be 37.8 L/h, with renal excretion accounting for approx. 58% of the total elimination. The vol. of distribution of the central compartment and the vol. of distribution at steady state were estd. to be 11.5L and 78.7L, resp. Individual pharmacokinetic parameter ests. were fixed in the pharmacodynamic model, where changes in heart rate were related to plasma drug concns. using a Michaelis-Menten model. The max. heart rate increase (Emax) and plasma regadenoson concn. causing a 50% increase in the max. heart rate (EC50) were estd. to be 76 beats per min and 12.3 ng/mL, resp. None of the tested covariates was found to be correlated with any of the pharmacokinetic model parameters. Conclusions: The pharmacokinetics and the effects of regadenoson on heart rate were successfully described using pharmacokinetic/pharmacodynamic modeling. The lack of a correlation between the model ests. and various baseline patient demographics supports unit-based dose administration of regadenoson. .