Disposition of the radioprotector ethiofos in the rhesus monkey. Influence of route of administration

Journal Article · Mon May 01 04:00:00 EDT 1989 · Drug Metabolism and Disposition; (USA)

OSTI ID:5600986

Mangold, D J; Miller, M A; Huelle, B K; Sanchez-Barona, D O; Swynnerton, N F; Fleckenstein, L; Ludden, T M ^[1]

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1. Southwest Research Institute, San Antonio, TX (USA)

Plasma concentrations of ethiofos (S-2-(3-aminopropylamino)ethyl phosphorothioic acid, WR-2721) were compared following iv, ip, intraduodenal, and portal administration to the rhesus monkey. Plasma samples were analyzed for ethiofos, free WR-1065, (2-(3-aminopropylamino)ethanethiol), and total material convertible to WR-1065 (total WR-1065). In separate experiments, total radioactivity in plasma was compared following iv, ip, and intraduodenal administration of ({sup 14}C)ethiofos; excretion of the radiolabel was measured in urine and in feces. Intraduodenal administration of unlabeled ethiofos rarely gave measurable levels of unchanged drug in plasma. In contrast, intraduodenal administration of ({sup 14}C)ethiofos produced an average AUC for total radioactivity that was 62% of that for a 10-min iv infusion of ({sup 14}C)ethiofos. Urinary excretion of radioactivity following iv and intraduodenal administration of ({sup 14}C)ethiofos was 78.9 +/- 14.0% and 43.8 +/- 12.4%, respectively, whereas 1.9 +/- 0.5% and 9.7 +/- 6.3% was excreted in feces. After an ip dose of either labeled or unlabeled ethiofos, absorption of the dose was prolonged, but AUC values for total radioactivity or ethiofos and total WR-1065 were similar to those observed after the corresponding 10-min iv experiments. For either iv or portal routes, increases in ethiofos AUC values were observed for the same total dose when the infusion rate was increased from 1.25 to 15 mg/kg/min.

• OSTI ID: 5600986
• Journal Information: Drug Metabolism and Disposition; (USA), Journal Name: Drug Metabolism and Disposition; (USA) Vol. 17:3; ISSN DMDSA; ISSN 0090-9556
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560152* -- Radiation Effects on Animals-- Animals
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
CARBON 14 COMPOUNDS
DRUGS
INJECTION
INTAKE
INTRAPERITONEAL INJECTION
INTRAVENOUS INJECTION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
METABOLISM
MONKEYS
PRIMATES
RADIOPROTECTIVE SUBSTANCES
TRACER TECHNIQUES
VERTEBRATES