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Biomedical subjects

T R Watson

Publications and source records attributed to T R Watson.

43 records · Page 3Linked to original sources
PubMedDate not supplied

4-Amino-3-(3'-methoxycarbonyl-2'-thioureido)benzophenone, a prodrug of mebendazole.

The compound 4-amino-3-(3'-methoxycarbonyl-2'-thioureido) benzophenone has shown promise as a prodrug of the anthelmintic mebendazole. The compound is stable in acid and neutral media and is rapidly hydrolysed in base. An HPLC assay procedure for mebendazole, the prodrug and their known or expected metabolites and degradation products in aqueous media and rat blood has been developed. The prodrug administrated orally to rats is rapidly converted to mebendazole. The area under the blood level versus time curve of mebendazole, in rats dosed with the prodrug, is more than twice that obtained after dosing rats with an equimolar amount of mebendazole. Only the prodrug, mebendazole and known metabolites of mebendazole are detected in rats dosed with the prodrug.

Animals↗
PubMedDate not supplied

The metabolic and pharmacokinetic disposition of mebendazole in the rat.

The metabolism and pharmacokinetics of mebendazole was studied in rats using [2'-3H]-mebendazole (biologically stable; specific activity 383.9 (mCi/mMol) and [2-14C]-mebendazole (specific activity 2.57 mCi/mMol). Analyses were performed by high pressure liquid chromatography and liquid scintillation spectrometry. About 85% of an intravenous dose was eliminated with the bile and the remainder with the urine. The majority of the dose was recovered as conjugated metabolites. The major metabolite (methyl-5(6)-(alpha-hydroxybenzyl)-2-benzimidazole carbamate) accounted for about 77% of the total recovered and 99% of it was conjugated. Anaerobic metabolism studies conducted in vitro with intestinal microorganisms obtained from rats indicated that metabolism of mebendazole did not occur in the gut, but that the intestinal microflora was able to hydrolyse conjugated metabolites which were eliminated with the bile. Mebendazole was found to have a biphasic elimination profile after intravenous administration. Its terminal plasma elimination half-life was 3.2 hours and its re-distribution half-life was 0.4 hour. After oral administration, as a solution in aqueous dimethyl sulphoxide, a bioavailability of 53% was obtained.

Administration, Oral↗
PubMedDate not supplied

The pharmacokinetics and tissue distribution of gomphoside in Wistar rats.

The excretion and tissue distribution of [3H]-gomphoside was studied after i.p. and i.v. administration of the cardiac glycoside (1 micrograms/g) to male Wistar rats. Following an intraperitoneal dosage of [3H]-gomphoside, most of the radioactivity (greater than 80%) had been excreted from the body by the end of 48 hours. Biliary excretion played a major role in elimination of [3H]-gomphoside with 90 +/- 15% of radioactivity being collected in 24 hours. Renal excretion formed a minor route of elimination of the cardiac glycoside; only 6 +/- 2% being excreted over 6 days. The distribution of radioactivity to tissues after an intravenous dose was rapid; most of the dose was located in the liver (32%), and the skeletal muscle (31%) 3 minutes after injection. The pharmacokinetics of [3H]-gomphoside could be described by a two-compartment open model with an average elimination half-life of 3.7 hours, and a large volume of distribution (2.3 +/- 0.3 ml/g body weight) characteristic of the commonly used cardiac glycosides (1).

Animals↗
PubMedDate not supplied

A rapid extraction method for acidic drugs in hemolyzed blood.

A simple and efficient method, based on the adsorption properties of octadecasilane bonded silica, is described for the rapid extraction of acidic drugs from whole post mortem blood. The blood was diluted, passed through an extraction column containing the bonded silica and the absorbed drugs were eluted with methanol. Following extraction into diethylether, the drugs were methylated and chromatographed. Recoveries were generally in excess of 80% at the microgram/mL level and the method substantially reduced the quantity of co-extracted lipids normally found in the acid extracts of hemolyzed blood. The procedure proved suitable for up to 2 mL blood and yielded clean extracts for gas chromatographic analysis.

Chromatography, Gas↗
PubMedDate not supplied

Three new contaminants detected in postmortem blood samples.

Three contaminants were identified during drug screening of postmortem blood samples which had been stored in glass bottles with a black rubber seal. Two of these contaminants, cyanoethyl dimethyldithiocarbamate and N-phenyl-2-naphthylamine, were found to come from the rubber seal of some bottles. The third contaminant was not a single compound but rather a mixture of aryl phosphates with a composition very similar to technical grade tritolyl phosphate. The origin of these phosphates is at present unknown.

2-Naphthylamine↗