Pharmacokinetics and material balance studies of diethylenetriamine trihydrochloride in the Fischer 344 rat following oral, endotracheal or intravenous dosing.
The metabolism and disposition of diethylenetriamine trihydrochloride (DETA.3HCl) were studied with regard to route of administration and dosage effects. Male Fischer 344 rats were administered 50 or 500 mg kg(-1) of [1,2-(14)C]-DETA.3HCl orally or endotracheally, and the fate of the 14C-radioactivity was followed for 48 h. The DETA.3HCl was readily absorbed from the gut or the lung, with bioavailabilities of 95% and 90%, respectively. It was distributed throughout the body, with the kidney attaining the highest concentration (about 2.5-5 times that of blood). The apparent volume of distribution determined from plasma concentration data following intravenous dosing (50 mg kg[-1]) was 486 ml kg(-1), consistent with distribution in the total body water. Urine and feces were the major routes of excretion, with only a small fraction eliminated as CO2. Excretion was quite rapid, with over 96% of the dose eliminated within 48 h. The principal component in the urine was unchanged DETA, suggesting that DETA.3HCl was not extensively metabolized. While the major metabolites has not been identified, there was evidence that DETA.3HCl was neither metabolized to ethylenediamine nor to the acid conjugates. There was indication that the metabolism of DETA.3HCl was saturated at 500 mg kg(-1), as there was a shift to a higher proportion of unchanged DETA excreted in the urine. There were no significant differences in material balance or pharmacokinetic parameters among animals receiving DETA.3HCl by the oral or endotracheal routes of administration.
Leung
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Health, Safety and Environment, Union Carbide Corporation, Danbury, CT 06817, USA.
Tyler
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D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002250:Carbon Radioisotopes; D002614:Chelating Agents / Q000493:pharmacokinetics; D005029:Ethylenediamines / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D007442:Intubation, Intratracheal; D008297:Male; D011073:Polyamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D014266:Trientine / Q000493:pharmacokinetics
D002250:Carbon Radioisotopes; D002614:Chelating Agents; D005029:Ethylenediamines; D011073:Polyamines; C005391:diethylenetriamine; C031234:ethylenediamine; D014266:Trientine