Lennox B. Turnbull

Excretion and Biotransformation of Carboxymethyl- cysteine in Rat, Dog, Monkey and Man

1. Following an oral dose of S-carboxymethyl [35S]cysteine monkey (rhesus and African green), rat, dog, and man excreted 77,88,95, and 100% respectively of the 35S radioactivity in urine and 7.0, 2.5, 0.7, and 0.3% in faeces during a 3 to 4 day period. 2. The principal drug-related components excreted were unchanged carboxymethylcysteine, dicarboxymethyl sulphide and inorganic sulphate. 3. Rat, dog, and man excreted primarily dicarboxymethyl sulphide and unchanged carboxymethylcysteine and no inorganic sulphate (rat, 7%). 4. Monkey excreted largely inorganic sulphate, moderate amounts of dicarboxymethyl sulphide and a trace of unchanged drug.

Mammalian degradation of (-)-nicotine to 3-pyridylacetic acid and other compounds.

Summary 1. The pattern of urinary excretion of C14 in the dog following intravenous administration of (-)-nicotine-C14 has been examined chromatographically by improved procedures. 2. The fractionated urine showed C14 activity corresponding chromatographically to the known metabolites: cotinine, γ- (3-pyridyl)-γ-methylaminobutyric acid, desmethylcotinine-hydroxycotinine, and γ-(3-pyridyl)-β-oxo-N-methylbutyramide. 3. Among many unidentified radioactive components, the urine contained material corresponding chromatographically to 3-pyridyl-acetic acid. 4. Following oral administration of (-)-cotinine to the dog. 3-pyridylacetic: acid was isolated from urine and characterized by analysis, melting point, mixed melting point and as its picric acid salt. 5. A precursor of 3-pyridylacetic acid is on formal grounds γ-(3-pyridyl)-β-oxobutyric acid, derivable from the known metabolite γ-(3-pyridyl)-β-oxo-N-methylbutyramide.

Butaperazine dimaleate metabolism

Abstract1. 2 - [1 - 14C]Butyryl - 10 - [3 - (4 - methylpiperazin - 1 - yl)propyl]phenothiazine (butaperazine) was synthesized and its metabolism, excretion and distribution studied in rats and dogs.2. A specific fluorescent method for butaperazine is described, and blood levels have been determined in dogs and humans following oral dosing.3. Two compounds, resulting from hydroxylation of the phenothiazine ring and N-demethylation, are the major metabolites. The sulphoxide, sulphone and a reduction product of the butyryl side chain carbonyl group are minor metabolites.4. The drug appears to be rapidly absorbed, undergoes biliary excretion and is excreted primarily in the faeces of rats and dogs.

The excretion and metabolism of triethylene glycol

A method is described for the preparation of randomly labeled triethylene glycol-C14. Methods are described for the colorimetric and vapor phase chromatographic determination of triethylene glycol in urine and for the determination of trace quantities of diethylene glycol in triethylene glycol. After oral doses of triethylene glycol the rat and the rabbit excrete triethylene glycol in both unchanged and oxidized form. The data suggest that one of the oxidation products is a monocarboxylic acid which arises by metabolic oxidation of a single terminal hydroxyl group of the parent glycol. After oral administration of triethylene glycol-C14 the rat eliminated only trace quantities of C14 activity as respiratory carbon dioxide. A small but measurable amount of radioactivity was found in the feces. The total elimination of radioactivity (in urine, feces, and expired air) during the 5-day period following a single oral dose (22.5 mg) was 91–98%. The major part of the radioactivity appeared in the urine. The data from fractionation of the urine indicated that only negligible quantities (if any) of C14 were present as oxalic acid. The major metabolic products had properties which suggested that triethylene glycol is degraded by the rcute: HOCH2CH2OCH2CH2OCH2CH2OH→ HOCH2CH2OCH2CH2OCH2COOH→HOOC CH2CH2OCH2CH2OCH2COOH The foregoing data, showing a high degree of elimination of triethylene glycol and its metabolites by way of the urine, is consistent with many findings pointing to the low or limited toxicity of triethylene glycol.

Metabolism of lactic acid and glycerol in C14-glyceryl lactopalmitate.

Summary 1. The fate of lactic acid-2-C14 following administration of glyceryl lacto-2-C14-palmitate was studied by converting lactate from blood or lymph to acetaldehyde which was counted as the dimedon derivative and as 2,2,7,7,9-pentamethyl-4,5-dioxo-octahydroxanthene. 2. The lactic acid content of lymph samples from the thoracic duct of the dog is subject to variation which arises from the speed with which samples are obtained through a cannula. 3. Appearance of radioactive CO2 in the expired air of rats following the administration of glyceryl lacto-2-C14-palmitate or glyceryl-1,3-C14-lactopalmitate, as well as the low fecal radioactivities, indicates a high degree of utilization of the fat. 4. In comparison with glycerol and glyceryl esters the metabolism of glyceryl-1-3-C14-lactopalmitate, as determined by the radioactivity of expired CO2, follows a path consistent with that expected from a normal ester of glycerol.