Biomaterial Database

The effect of a high-fat meal on the pharmacodynamics of a model lipophilic compound that binds extensively to triglyceride-rich lipoproteins. 2007

Pavel Gershkovich, and Daniel Shtainer, and Amnon Hoffman

Department of Pharmaceutics, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.

A high-fat meal induces transient hyperlipidemia characterized by elevated triglyceride-rich lipoproteins (TRL) which are composed mainly of chylomicrons. The purpose of this work was to investigate the effect of this transient hyperlipidemia on the pharmacodynamics of lipophilic drugs, using DDT as a model compound since it binds extensively to TRL and has a distinct neurotoxic effect. The postprandial hyperlipidemia in rats was induced by oral administration of peanut oil and was monitored by measurement of plasma triglyceride levels. The control group received water instead of oil. The rats received a continuous intravenous infusion of DDT (10 mg/h) until onset of a predefined pharmacodynamic endpoint (facial muscle tremor). Plasma and brain samples were then obtained and assayed for DDT. Rats with postprandial hyperlipidemia required higher dose of DDT to induce onset of facial muscle tremor. At the pharmacodynamic endpoint, oil treated rats had significantly higher concentrations of DDT in plasma and in the chylomicron fraction, but DDT brain concentrations were the same in both groups. In conclusion, a high-fat meal induces postprandial hyperlipidemia that may significantly alter the pharmacological profile of lipophilic compounds that bind to TRL. This is due to alteration of the distribution characteristics of the lipophilic compound through its association with postprandial lipoproteins. However, this pharmacokinetic phenomenon did not affect the concentration-effect relationship at the site of action in the brain.

UI	MeSH Term	Description	Entries
D006949	Hyperlipidemias	Conditions with excess LIPIDS in the blood.	Hyperlipemia,Hyperlipidemia,Lipemia,Lipidemia,Hyperlipemias,Lipemias,Lipidemias
D007262	Infusions, Intravenous	The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.	Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D008297	Male		Males
D010938	Plant Oils	Oils derived from plants or plant products.	Oils, Plant,Oils, Vegetable,Plant Oil,Vegetable Oil,Vegetable Oils,Oil, Plant,Oil, Vegetable
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
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
D002914	Chylomicrons	A class of lipoproteins that carry dietary CHOLESTEROL and TRIGLYCERIDES from the SMALL INTESTINE to the tissues. Their density (0.93-1.006 g/ml) is the same as that of VERY-LOW-DENSITY LIPOPROTEINS.	Chylomicron
D003634	DDT	A polychlorinated pesticide that is resistant to destruction by light and oxidation. Its unusual stability has resulted in difficulties in residue removal from water, soil, and foodstuffs. This substance may reasonably be anticipated to be a carcinogen: Fourth Annual Report on Carcinogens (NTP-85-002, 1985). (From Merck Index, 11th ed)	1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane,4,4'-DDT,4,4'-Dichlorodiphenyltrichloroethane,Benzochloryl,Chlorophenothane,TbisC-ethane,p',p'-DDT,4,4' DDT,4,4' Dichlorodiphenyltrichloroethane,TbisC ethane
D004041	Dietary Fats	Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados.	Fats, Dietary,Dietary Fat,Fat, Dietary
D005152	Facial Muscles	Muscles of facial expression or mimetic muscles that include the numerous muscles supplied by the facial nerve that are attached to and move the skin of the face. (From Stedman, 25th ed)	Mimetic Muscles,Facial Muscle,Mimetic Muscle,Muscle, Facial,Muscle, Mimetic,Muscles, Facial,Muscles, Mimetic