Hepatic and muscle clearance of physostigmine in the rat after i. v. administration

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5384707

Somani, S M; Unni, L K

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-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALOIDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL HALF-LIFE
BIOLOGICAL MATERIALS
BLOOD
BLOOD FLOW
BLOOD PLASMA
BODY
BODY FLUIDS
CHROMATOGRAPHY
CLEARANCE
DIGESTIVE SYSTEM
DRUGS
ESERINE
GLANDS
INJECTION
INTAKE
INTRAVENOUS INJECTION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
LIVER
MAMMALS
MATERIALS
METABOLISM
METABOLITES
MUSCLES
ORGANIC COMPOUNDS
ORGANS
PARASYMPATHOMIMETICS
RATS
REACTION KINETICS
RODENTS
SEPARATION PROCESSES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES