Biomaterial Database

A physiologically based pharmacokinetic and pharmacodynamic model for paraoxon in rainbow trout. 1997

R Abbas, and W L Hayton

Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus 43210-1291, USA.

Trout were exposed to an aqueous solution of 75 ng/ml paraoxon for 5 days at 12 degrees C. The relationships among paraoxon concentration in water and target organs, AChE inhibition, and carboxylesterase (CaE) detoxification of paraoxon were characterized quantitatively by development of a PBPK-PD model. The PKPD model structure consisted of brain, heart, liver, kidney, and remainder of the body, which were interconnected by blood circulation. The paraoxon tissue/blood partition coefficients were: plasma/water, 1.46; liver/plasma, 5.89; brain/plasma, 3.90; heart/plasma, 2.91; kidney/plasma, 0.45; and blood/plasma, 0.91. Turnover of AChE was characterized from a dose-response study, in which its zero-order synthesis rate and first-order degradation rate constant were determined in several tissues; for brain they were 7.67 pmol/min and 7.31 x 10(-5) hr(-1). The uptake and depuration clearances of paraoxon (Cl(u) = 0.651 and Cl(d) = 0.468 ml min(-1) g body wt(-1)) were determined using a compartmental model. During continuous water exposure to paraoxon, AChE activity in the tissues declined to new steady state values that were maintained by the synthesis of new AChE. CaE was shown by simulation to be an important pathway for detoxification of paraoxon.

UI	MeSH Term	Description	Entries
D007306	Insecticides	Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics.	Insecticide
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
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
D009206	Myocardium	The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.	Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010261	Paraoxon	An organophosphate cholinesterase inhibitor that is used as a pesticide.	Diethyl-p-Nitrophenyl Phosphate,E-600,Fosfakol,Phosphacol,Diethyl p Nitrophenyl Phosphate,E 600,E600,Phosphate, Diethyl-p-Nitrophenyl
D011786	Quality Control	A system for verifying and maintaining a desired level of quality in a product or process by careful planning, use of proper equipment, continued inspection, and corrective action as required. (Random House Unabridged Dictionary, 2d ed)	Control, Quality,Controls, Quality,Quality Controls
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D002265	Carboxylic Ester Hydrolases	Enzymes which catalyze the hydrolysis of carboxylic acid esters with the formation of an alcohol and a carboxylic acid anion.	Carboxylesterases,Ester Hydrolases, Carboxylic,Hydrolases, Carboxylic Ester