Biomedical subjects

A M Hackett

Publications and source records attributed to A M Hackett.

22 records · Page 2Linked to original sources

PubMed1977

The disposition and metabolism of 3',4',7-tri-O-(beta-hydroxyethyl)rutoside and 7-mono-O-(beta-hydroxyethyl)rutoside in the mouse.

1. Following intravenous administration of 3',4',7-tri-O-(beta-hydroxy[14C2]ethyl)rutoside or 7-mono-O-(beta-hydroxy[14C2]ethyl)rutoside to male mice, 68% of the dose of each is excreted in faeces as the corresponding hydroxyethyl-quercetin within 72 h of dosage. Mean urinary excretions of mono- and tri-hydroxyethylrutosides in 72 h were 27 and 21% respectively. Unchanged rutosides and their glucuronides were detected in urine. 2. In biliary-cannulated animals, the mean biliary excretion of both tri- and mono-hydroxyethylrutosides was 71%, in 24 h of dosage. In both cases most 14C was excreted in 3 h, as unchanged rutosides and glucuronide conjugates. 3. Fall of blood 14C concn, was rapid for both compounds. Neither compound was detected in brain but there was short-term accumulation in liver and kidney, and 2--3 h after dosage, most 14C for both compounds was associated with the gastro-intestinal contents. 4. Animals killed 72 h after dosage of either compound contained less than 7% of dose, mostly in the colon and caecal contents. 5. Foetuses removed 3 h after dosage of either compound to the dams did not contain 14C; foetuses removed 5 min after dosage contained low levels of 14C, substantially below the maternal blood level and equiv. to less than 0-1% of dose in each case. No 14C was detected in amniotic fluid.

Animals↗

PubMed1976

Metabolism of hydroxyethylrutosides (HR): metabolism of [14C]-HR in man.

1. following oral administration of a [14C]-hydroxyethylrutoside (Paroven, Venoruton) preparation (HR) to three subjects, 3.05--5.97% of the administered [14C] was excreted in urine. Unchanged urinary [14C]-hydroxyethylrutosides represented 1.57--1.96% of the total dose. 2. Significant levels of [14C] were detected in plasma within 1 h of oral administration of HR. Peak levels were observed from 2--9 h. 3. The presence in urine of [14C]-3',4',5,7-tetra-O-(beta-hydroxyethyl)rutoside, [14C]-3',4',7-tri-O-(beta-hydroxyethyl)rutoside and [14C]-4',7-di-O-(beta-hydroxyethyl)rutoside was shown by radioscanning and/or spectal methods. 4. Administration of a second oral dose of [14C]-HR to each of the three subjects following extended dosage of nonlabelled HR did not result in any increase in urinary [14C] excretion over that observed after administration of a single oral dose. 5. Observations on urinary excretion in man are compatible with the finding in experimental animals that the major route of hydroxyethylrutoside excretion is via the biliary-enteric route.

Administration, Oral↗

PubMedDate not supplied

The metabolism and excretion of 3-O-methyl-(+)-catechin in the rat, mouse, and marmoset.

Following oral or intravenous administration to the rat, 3-O-methyl-(+)-catechin was metabolized by methylation of a B-ring phenolic hydroxyl group to 3,3'(or 4')-dimethyl-(+)-catechin, which was further conjugated with glucuronic acid and excreted both in urine and bile. Small amounts of unchanged 3-O-methyl-(+)-catechin was excreted in rat urine following parenteral but not oral administration. Excretion of radioactivity following parenteral administration of 3-O-[14C]methyl-(+)-catechin to the rat and marmoset was similar (approximately 50% in urine and 35% in feces). The mouse excreted 79% of radioactivity in urine and 22% in feces. Radioactivity in mouse and marmoset urine was associated with free dimethyl-(+)-catechin rather than the glucuronide conjugate prevalent in rat urine. Following oral administration to the marmoset, urinary excretion of 14C was lower than in the rat and again the major metabolite was the free dimethyl-(+)-catechin. In bile duct-cannulated rats approximately half of administered radioactivity was excreted in bile. In each experiment more than 85% of the 14C in bile was in the form of dimethylcatechin glucuronide. It is concluded that biological methylation is the major route of 3-O-methyl(+)-catechin metabolism in all species investigated, and that the compound does not undergo ring fission as has been reported in respect of the parent compound, (+)-catechin.

Administration, Oral↗

PubMedDate not supplied

The effects of an experimental hepatitis on the metabolic disposition of 3-o-(+)-[14C]methylcatechin in the rat.

The induction of an experimental hepatitis did not affect the overall ability of the rat to metabolize the flavanol 3-O-(+)-[14C]methylcatechin by methylation or glucuronidation. The induction of hepatitis did cause a significant increase in metabolite excretion in urine (from 52% of the dose in control rats to 88% in hepatitis). Fecal excretion was correspondingly depressed (44 to 4% of the dose). In bile duct-cannulated rats, the induction of hepatitis prior to 3-O-(+)-[14C]methylcatechin administration resulted in low 14C excretion (38%) in bile (cf. 58% in bile of controls). The data obtained indicate that following induction of hepatitis biliary metabolites reabsorbed from the intestine are not reexcreted in bile in an enterohepatic cycle as in the normal rat but are excreted via the kidney. Induction of hepatitis did not affect the fast clearance of unchanged 3-O-methyl-(+)-catechin from plasma but plasma clearance of the metabolites was reduced from 112 to 89 ml/hr.

Animals↗