Biomaterial Database

Systemic intestinal metabolism of 1-naphthol. A study in the isolated vascularly perfused rat small intestine. 1989

M H de Vries, and G A Hofman, and A S Koster, and J Noordhoek

Department of Pharmacology, Faculty of Pharmacy, University of Utrecht, The Netherlands.

Using a vascularly and luminally perfused rat small intestine, we studied the systemic intestinal metabolism of the model substrate 1-naphthol (1-N) to 1-naphthol-beta-D-glucuronide (1-NG). An intestinal extraction ratio of 0.30 +/- 0.02 was found for 1-N. This implies that intestinal metabolism represents up to 14% of the total plasma clearance of 1-N in the rat in vivo. The formed 1-NG was preferentially released into the vascular perfusate, suggesting specialized transport carriers for 1-NG in brushborder and basolateral membrane. When the vascular flow rate was decreased from 10 to 0.5 ml/min, the clearance of 1-N appeared to be completely flow dependent. The apparent conflict between a low extraction ratio (0.30 +/- 0.02 at all flows investigated) and a flow rate-limited 1-N clearance can be explained by the presence of an intestinal vascular bed with a high extraction ratio. We suggest that 1-N is completely extracted from the mucosal blood flow. This view was confirmed by the results of experiments in which the capillary flow of the intestinal mucosa was decreased by infusion of noradrenaline. As a result a temporary decrease in the 1-N extraction ratio was observed. The contribution of the intestine to the total clearance can be masked by the hepatic clearance, because the blood supply to the intestine and liver is coupled in series. An equation was derived to describe the relative contribution of the intestine to the mesenteric clearance of the intestine-liver system. It appears that the effective contribution of the intestine to the mesenteric clearance is of little interest for high extraction drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D007421	Intestine, Small	The portion of the GASTROINTESTINAL TRACT between the PYLORUS of the STOMACH and the ILEOCECAL VALVE of the LARGE INTESTINE. It is divisible into three portions: the DUODENUM, the JEJUNUM, and the ILEUM.	Small Intestine,Intestines, Small,Small Intestines
D008297	Male		Males
D008638	Mesenteric Arteries	Arteries which arise from the abdominal aorta and distribute to most of the intestines.	Arteries, Mesenteric,Artery, Mesenteric,Mesenteric Artery
D008657	Metabolic Clearance Rate	Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.	Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
D009284	Naphthols	Naphthalene derivatives carrying one or more hydroxyl (-OH) groups at any ring position. They are often used in dyes and pigments, as antioxidants for rubber, fats, and oils, as insecticides, in pharmaceuticals, and in numerous other applications.	Hydroxynaphthalene,Hydroxynaphthalenes,Naphthol
D009638	Norepinephrine	Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic.	Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010477	Perfusion	Treatment process involving the injection of fluid into an organ or tissue.	Perfusions
D011919	Rats, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.	August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001783	Blood Flow Velocity	A value equal to the total volume flow divided by the cross-sectional area of the vascular bed.	Blood Flow Velocities,Flow Velocities, Blood,Flow Velocity, Blood,Velocities, Blood Flow,Velocity, Blood Flow
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response