Hepatic and muscle clearance of physostigmine in the rat after i. v. administration
This study presents a method to calculate the extraction ratio (ER) from in vivo time course of liver metabolism using the physiological and pharmacokinetic parameters such as plasma flow rate, partition coefficient of drug between tissue and plasma and the elimination rate constant from tissues. Rats were administered /sup 3/H-physostigmine (Phy), 100 ..mu..g/kg i.v.; and were sacrificed at various times. Tissues were removed and Phy and its metabolites were determined by HPLC. Half-life of Phy in liver and muscle was 24 and 20 min, respectively. ER of Phy in liver was .71 which showed a slight decrease at 10 min. Muscle ER was found to be .347 up to 5 min. Hepatic clearance was calculated to be 23.08 ml/min/kg (34.9% of systemic clearance) and the intrinsic clearance was 83.73 ml/min/kg which indicates that the changes in blood flow to the liver can cause a variation in the systematic clearance. Percentage dose of Phy retained in muscle was maximum and the clearance was 5.2 ml/min/kg suggesting that muscle might be acting as a storage depot for Phy prolonging the pharmacological effects. About 30-40% of radioactivity in the liver could not be washed off by 10% TCA or organic solvents indicating the irreversible binding of drug or metabolite to liver macromolecule.
- Research Organization:
- Southern Illinois Univ. School of Medicine, Springfield
- OSTI ID:
- 5384707
- Report Number(s):
- CONF-8604222-; TRN: 86-026654
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ESERINE
CLEARANCE
METABOLISM
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL HALF-LIFE
BLOOD FLOW
BLOOD PLASMA
INTRAVENOUS INJECTION
LIQUID COLUMN CHROMATOGRAPHY
LIVER
METABOLITES
MUSCLES
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALOIDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL MATERIALS
BLOOD
BODY
BODY FLUIDS
CHROMATOGRAPHY
DIGESTIVE SYSTEM
DRUGS
GLANDS
INJECTION
INTAKE
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
ORGANIC COMPOUNDS
ORGANS
PARASYMPATHOMIMETICS
REACTION KINETICS
RODENTS
SEPARATION PROCESSES
VERTEBRATES
550501* - Metabolism- Tracer Techniques