Biomaterial Database

Stereoselective disposition and metabolism of pinacidil in rat. 1994

K Sakamoto, and Y Nakamura

Kanzakigawa Laboratory, Shionogi Research Laboratories, Shionogi & Co., Ltd, Osaka, Japan.

1. An hplc method has been established for the determination of the enantiomer ratios of pinacidil and pinacidil-pyridine-N-oxide (M-1), using a beta-cyclodextrin-containing mobile phase. 2. Shortly after the administration of racemic pinacidil (2 mg/kg, i.v. or oral) to rat, the enantiomer ((+)/(-)) ratios of pinacidil in plasma were about 1 (i.v.) or > 1 (oral), whereas those of M-1 were < 1; both ratios increased with time. The (+)/(-) ratios of M-1 and pinacidil in 0.24 h urine samples were 0.65 (i.v.), 0.63 (oral), and 2.09 (i.v.), and 1.56 (oral), respectively, in male rat, and 0.76 (i.v.), 0.77 (oral) and 1.79 (i.v.), and 1.48 (oral), respectively, in female rat. 3. No isomerization of (+)- or (-)-pinacidil was observed during incubation with liver slices, and there was no stereoselectivity in the protein binding of the drug. An (-)-enantiomer-rich M-1, however, was produced after incubation of (+/-)-pinacidil with liver slices. The N-oxidation of (-)-pinacidil exhibited a higher stereoselectivity in males than females (the (+)/(-) ratio of M-1 in male, 0.55; female, 0.68). 4. These results indicated that the stereoselective disposition of pinacidil in rat was due, in large part, to the stereoselective N-oxidation of this drug in the liver.

UI	MeSH Term	Description	Entries
D007275	Injections, Intravenous	Injections made into a vein for therapeutic or experimental purposes.	Intravenous Injections,Injection, Intravenous,Intravenous Injection
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008297	Male		Males
D008433	Mathematics	The deductive study of shape, quantity, and dependence. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)	Mathematic
D008657	Metabolic Clearance Rate	Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.	Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
D008962	Models, Theoretical	Theoretical representations that simulate the behavior or activity of systems, processes, or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.	Experimental Model,Experimental Models,Mathematical Model,Model, Experimental,Models (Theoretical),Models, Experimental,Models, Theoretic,Theoretical Study,Mathematical Models,Model (Theoretical),Model, Mathematical,Model, Theoretical,Models, Mathematical,Studies, Theoretical,Study, Theoretical,Theoretical Model,Theoretical Models,Theoretical Studies
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D005260	Female		Females
D006146	Guanidines	A family of iminourea derivatives. The parent compound has been isolated from mushrooms, corn germ, rice hulls, mussels, earthworms, and turnip juice. Derivatives may have antiviral and antifungal properties.
D000284	Administration, Oral	The giving of drugs, chemicals, or other substances by mouth.	Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations