Bioavailability and disposition kinetics of HI-6 in Beagle dogs. 1993

J D Baggot, and A Buckpitt, and D Johnson, and P Brennan, and H Chung
Department of Pharmacology and Toxicology School of Veterinary Medicine, Johnstown, Co Kildare, Ireland.

The absorption and disposition kinetics of HI-6 were determined in Beagle dogs given single doses (25 mg kg-1) of the drug by the intravenous, intramuscular, and oral routes. Concentrations of the oxime in plasma and urine were measured by HPLC. A two-compartment open model was used to describe the disposition curve following intravenous drug administration while a one-compartment open model with first-order absorption adequately described the data following intramuscular or oral administration of the dose. Extravascular distribution of HI-6 was limited (Vss 203 ml kg-1) and the drug was eliminated rapidly after intravenous administration (t1/2 46.5 min, MAT 55.4 min). Systemic clearance was 3.68 ml min-1 x kg. A major fraction of the dose (63.7 per cent) was excreted in urine over a 24-h collection period. Following intramuscular drug administration, the absorption half-life (t1/2(a), 5.3 min), MAT (17.1 min), Cmax (70.37 micrograms ml-1) and tmax (15.9 min) indicate that the drug was rapidly absorbed. Systemic availability was 83.43 per cent after oral drug administration, absorption was preceded by a lag time (23.2 min). The t1/2(a) (41.5 min), MAT (81.6 min), Cmax (4.30 micrograms ml-1) and Tmax (90.6 min) indicate somewhat delayed absorption. Systemic availability (11.38 per cent) and the fraction of dose excreted unchanged in the urine (9.3 per cent) show that the drug was poorly absorbed. The apparent half-life (58.0 min) and MRT (137.6 min) following oral administration were significantly longer (p < 0.05) than following intravenous or intramuscular administration suggesting that the rate of absorption from the gastrointestinal tract decreases the elimination rate of the drug. In conclusion, HI-6 has limited distribution within the body, is rapidly eliminated mainly by renal excretion unchanged in the urine, and the bioavailability (i.e. rate and extent of absorption) of the drug varies with the route of administration.

UI MeSH Term Description Entries
D007273 Injections, Intramuscular Forceful administration into a muscle of liquid medication, nutrient, or other fluid through a hollow needle piercing the muscle and any tissue covering it. Intramuscular Injections,Injection, Intramuscular,Intramuscular Injection
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D010091 Oximes Compounds that contain the radical R2C Aldoximes,Hydroxyimino Compounds,Ketoxime,Ketoximes,Oxime,Compounds, Hydroxyimino
D011726 Pyridinium Compounds Derivatives of PYRIDINE containing a cation C5H5NH or radical C5H6N. Compounds, Pyridinium
D002801 Cholinesterase Reactivators Drugs used to reverse the inactivation of cholinesterase caused by organophosphates or sulfonates. They are an important component of therapy in agricultural, industrial, and military poisonings by organophosphates and sulfonates. Insecticides, Organophosphate, Antagonists,Insecticides, Organothiophosphate, Antagonists,Organophosphate Insecticide Antagonists,Organothiophosphate Insecticide Antagonists,Antagonists, Organophosphate Insecticide,Antagonists, Organothiophosphate Insecticide,Insecticide Antagonists, Organophosphate,Insecticide Antagonists, Organothiophosphate,Reactivators, Cholinesterase
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
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
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
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

Related Publications

J D Baggot, and A Buckpitt, and D Johnson, and P Brennan, and H Chung
September 1980, Toxicology and applied pharmacology,
J D Baggot, and A Buckpitt, and D Johnson, and P Brennan, and H Chung
January 1983, Biopharmaceutics & drug disposition,
J D Baggot, and A Buckpitt, and D Johnson, and P Brennan, and H Chung
February 1987, Journal of pharmacokinetics and biopharmaceutics,
J D Baggot, and A Buckpitt, and D Johnson, and P Brennan, and H Chung
May 1988, Journal of pharmaceutical sciences,
J D Baggot, and A Buckpitt, and D Johnson, and P Brennan, and H Chung
October 1977, Canadian journal of comparative medicine : Revue canadienne de medecine comparee,
J D Baggot, and A Buckpitt, and D Johnson, and P Brennan, and H Chung
January 1983, Drug metabolism and disposition: the biological fate of chemicals,
J D Baggot, and A Buckpitt, and D Johnson, and P Brennan, and H Chung
November 1987, Toxicology letters,
J D Baggot, and A Buckpitt, and D Johnson, and P Brennan, and H Chung
August 2009, Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica,
J D Baggot, and A Buckpitt, and D Johnson, and P Brennan, and H Chung
January 1981, Chemical & pharmaceutical bulletin,
Copied contents to your clipboard!