Disposition of the radioprotector ethiofos in the rhesus monkey. Influence of route of administration.
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 [14C]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 [14C]ethiofos produced an average AUC for total radioactivity that was 62% of that for a 10-min iv infusion of [14C]ethiofos. Urinary excretion of radioactivity following iv and intraduodenal administration of [14C]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.(ABSTRACT TRUNCATED AT 250 WORDS)
Mangold
D J
DJ
Department of Applied Chemistry and Chemical Engineering, Southwest Research Institute, San Antonio, TX 78284.
Miller
M A
MA
Huelle
B K
BK
Sanchez-Barona
D O
DO
Swynnerton
N F
NF
Fleckenstein
L
L
Ludden
T M
TM
D004999:Amifostine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007441:Intubation, Gastrointestinal; D008253:Macaca mulatta; D008297:Male; D009946:Organothiophosphorus Compounds / Q000493:pharmacokinetics*; D011169:Portal Vein; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; D004999:Amifostine