Pharmacokinetics and toxicity of the oxime HGG 12 in dogs. 1985

R Klimmek, and P Eyer

The pharmacokinetics, pharmacodynamics, and toxicity of the oxime HGG 12 were studied in conscious and anesthetized dogs. IV administration. The mean value of the half-time for terminal elimination of HGG 12 was 47 min; plasma clearance amounted to 4.6 ml kg-1 min-1 and Vapp to 0.315 1 kg-1. At doses above 1 mumol/kg heart rate, left ventricular pressure and mean arterial pressure decreased, while central venous pressure and femoral blood flow increased. The dose-response curves were very flat. Repetitive administration of various doses of HGG 12 in 30 min intervals did not enhance the negative chronotropic effect when the preceding total dose amounted to about 1 mumol/kg. IM administration. The half-times for the absorption of HGG 12 dichloride and HGG 12 dinitrate were about 3.5 min; the corresponding value for HGG 12 dibromide was 9.4 min. In the elimination phase the half-time was comparable with that of the IV experiments. About 60% of the oxime was excreted unchanged in the urine within 24 h. The circulatory changes showed the same tendency as after IV injection. Conscious dogs tolerated well daily doses of 10 mumol/kg for 6 weeks. At 30 mumol/kg all dogs survived, displaying symptoms reminiscent of a cholinergic syndrome. Five out of eight dogs survived at 90 mumol/kg. Macroscopic and microscopic examinations and blood chemistry data showed no abnormality.

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
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D011726 Pyridinium Compounds Derivatives of PYRIDINE containing a cation C5H5NH or radical C5H6N. Compounds, Pyridinium
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
D005260 Female Females
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D000758 Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures.
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

Related Publications

R Klimmek, and P Eyer
January 1979, Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement,
R Klimmek, and P Eyer
September 2022, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association,
R Klimmek, and P Eyer
November 1992, Pharmacology & toxicology,
R Klimmek, and P Eyer
August 2012, Journal of veterinary pharmacology and therapeutics,
R Klimmek, and P Eyer
January 1996, Cancer chemotherapy and pharmacology,
R Klimmek, and P Eyer
January 2016, Advances in therapy,
R Klimmek, and P Eyer
April 1984, Fundamental and applied toxicology : official journal of the Society of Toxicology,
R Klimmek, and P Eyer
January 1995, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group,
Copied contents to your clipboard!