Track topics on Twitter Track topics that are important to you
1. 7-Methoxy-6-(3-methoxy-benzyloxy)-2-methylisoquinolin-1(2H)-one (named as IS0042) is a newly identified melatoninergic agonist which exhibits selectivity to the type 2 melatonin receptor. Here, we examined the in vitro and in vivo pharmacokinetics properties of IS0042 in rats. 2. IS0042 was considerably lipophilic with a modest aqueous solubility of 27.3 µg/mL. It was stable in simulated gastrointestinal fluid, and readily penetrated across differentiated Caco-2 cell model of intestinal barrier, suggesting good oral absorption. 3. IS0042 underwent metabolism in rat intestinal and liver microsomes with an in vitro half-life of 367.5 ± 36.6 and 17.5 ± 2.7 min, respectively. Metabolite identification suggested that the major biotransformation pathways included the cleavage of ether bond, hydroxylation and demethylation. The same metabolites were also present in blood circulation following oral administration, indicating a good correlation between in vitro and in vivo metabolism. 4. The pharmacokinetics parameters of IS0042 were evaluated after intravenous administration (10 or 25 mg/kg) and oral administration (100 mg/kg) of the drug to rats. IS0042 showed moderate clearance (0.73-1.02 L/h/kg), large volume of distribution (1.76-3.16 L/kg) and long elimination half-life (3.11-6.04 h) after intravenous administration. The absolute oral bioavailability of IS0042 was relatively low (9.8-18.6%). Overall, these results provide important parameters for the further development of this novel class of melatoninergic ligands.
Division of Life Sciences, and the Biotechnology Research Institute, Hong Kong University of Science and Technology , Clear Water Bay, Kowloon, Hong Kong , China.
This article was published in the following journal.
Name: Xenobiotica; the fate of foreign compounds in biological systems
This study was designed to investigate the effects of cilostazol on the pharmacokinetics of carvedilol following oral or intravenous administration of carvedilol in rats. Clinically carvedilol and cil...
Pimobendan is a benzimidazole-pyridazinone derivative, marketed as a racemic mixture for the management of canine heart failure. Pharmacokinetics of the enantiomers of pimobendan and its oral bioavail...
Entacapone is an inhibitor of catechol-O-methyltransferase (COMT) and is being used to extend the therapeutic effect of levodopa in patients with advanced and fluctuating Parkinson's disease. Entacapo...
To develop a novel self-nanoemulsifying drug delivery system (solid SNEDDS) with better oral bioavailability of tacrolimus, the solid SNEDDS was obtained by spray-drying the solutions containing the l...
Silibinin, the main active component of Silybum marianum is a hepatoprotective and antioxidant agent with antitumour effect, exhibiting very low aqueous solubility and oral bioavailability limiting it...
The main purpose of this study was to evaluate the effects of melatonin in the regulation of the vascular injury in smokers through population-based, randomized, double-blind, placebo-cont...
Effect of Melatonin on Body Composition, Glucose Metabolism and Lipid Metabolism.
The primary focus of this five-year study will be to optimize the melatonin dosing regimen for synchronizing the body clocks of blind children to the 24-hour day.
Morbid obesity (MO) is associated with several disorders such as hypertension, type 2 diabetes, dyslipemia and degenerative arthropathy that require pharmacological treatment. Drug bioavai...
Atypical antipsychotic medications, such as olanzapine, cause metabolic side effects, including weight gain, extra fat around the middle of the body, high blood sugar, and high cholesterol...
A biogenic amine that is found in animals and plants. In mammals, melatonin is produced by the PINEAL GLAND. Its secretion increases in darkness and decreases during exposure to light. Melatonin is implicated in the regulation of SLEEP, mood, and REPRODUCTION. Melatonin is also an effective antioxidant.
A family of G-protein-coupled receptors that are specific for and mediate the effects of MELATONIN. Activation of melatonin receptors has been associated with decreased intracellular CYCLIC AMP and increased hydrolysis of PHOSPHOINOSITIDES.
A potent and specific HIV protease inhibitor that appears to have good oral bioavailability.
Agents that aid or increase the action of the principle drug (DRUG SYNERGISM) or that affect the absorption, mechanism of action, metabolism, or excretion of the primary drug (PHARMACOKINETICS) in such a way as to enhance its effects.
A melatonin receptor subtype primarily found expressed in the BRAIN and RETINA.
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...