Biomaterial Database

Pharmacokinetics and metabolism of isosorbide-dinitrate after intravenous and oral administration. 1985

U Abshagen, and G Betzien, and R Endele, and B Kaufmann, and G Neugebauer

The bioavailabilities of a conventional and two slow release 20 mg isosorbide dinitrate (ISDN) formulations were compared after oral administration in a three way cross-over study in 8 male volunteers. In a further group of 6 male volunteers the pharmacokinetics and metabolism of ISDN were investigated after intravenous infusion of a median dose of 14.1 mg for 2.5 h. A new analytical procedure was developed for the determination of isosorbide-5-mononitrate-2-glucuronide (IS-5-MN-2-Glu) and of isosorbide (IS). Kinetic data analysis on a molar basis was performed by the program package KIN-PAK providing model independent parameters. The median elimination half-lives of ISDN, IS-5-MN, IS-2-MN and IS-5-MN-2-Glu were 0.7, 5.1, 3.2 and 2.5 h, respectively. The systemic clearance of ISDN was 3.71/min and the distribution volume 2521 (3.1 l/kg). Apart from IS-5-MN-2-Glu, with a renal clearance of 5.9 l/min which suggested substantial glucuronidation in the kidney, the renal clearances of ISDN, IS-5-MN, IS-2-MN and the corresponding amounts excreted were negligible. 27.8% of the administered ISDN was excreted as IS-5-MN-2-Glu (8.7%) and IS (19.1%). Calculations based on the two mononitrate metabolites formed from ISDN showed an incomplete recovery of 84.1%, leading to the assumption that a simultaneous denitration to IS must have occurred. The rate of denitration at each nitro group in ISDN was almost twice as high as for the same position in the corresponding mononitrate.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D007263	Infusions, Parenteral	The administration of liquid medication, nutrient, or other fluid through some other route than the alimentary canal, usually over minutes or hours, either by gravity flow or often by infusion pumping.	Intra-Abdominal Infusions,Intraperitoneal Infusions,Parenteral Infusions,Peritoneal Infusions,Infusion, Intra-Abdominal,Infusion, Intraperitoneal,Infusion, Parenteral,Infusion, Peritoneal,Infusions, Intra-Abdominal,Infusions, Intraperitoneal,Infusions, Peritoneal,Intra Abdominal Infusions,Intra-Abdominal Infusion,Intraperitoneal Infusion,Parenteral Infusion,Peritoneal Infusion
D007548	Isosorbide Dinitrate	A vasodilator used in the treatment of ANGINA PECTORIS. Its actions are similar to NITROGLYCERIN but with a slower onset of action.	Cardonit 40,Dilatrate,Iso-Bid,Isodinit,Isoket,Isoket Retard-120,Isomak R,Isordil,Isotrate,Nitrosorbide,Sorbitrate,Sorbonit,Dinitrate, Isosorbide,Iso Bid,IsoBid,Isoket Retard 120,Isoket Retard120
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008297	Male		Males
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D001682	Biological Availability	The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.	Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities