Pharmacokinetics of WR-1065 in mouse tissue following treatment with WR-2721.
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| Abstract |
Levels of reduced glutathione (GSH) and N-(2-mercaptoethyl)-1,3-diaminopropane (WR-1065) were measured in tissues of Balb/c mouse bearing EMT6 tumors at time intervals ranging from 5 min to 48 hr after i.v. injection of S-2-(3-aminopropylamino)ethyl phosphorothioate (WR-2721) at 500 mg per kg. In all tissues examined (liver, kidney, lung, heart, muscle, brain, tumor, spleen, and salivary gland), maximal WR-1065 levels occurred 5-15 min after injection, with levels in liver, kidney, lung, and salivary gland exceeding one mumole per gm. The post-maximum decline in WR-1065 varied markedly with tissue, lung exhibiting a 6-fold drop by 30 min and salivary gland falling only 15% after 3 hr. In a mouse treated with carbon-14 labeled WR-2721 it was found after 15 min that WR-1065 accounted for over half of the total drug in all tissues except tumor, where it accounted for a third of the total drug. There was no evidence that GSH levels were substantially altered by WR-2721 treatment. The results provide the first direct evidence supporting the widely held view that WR-2721 treatment results in intracellular WR-1065 and they demonstrate that high levels of WR-1065 occur very soon after i.v. injection.
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| Authors | J F Utley, N Seaver, G L Newton, R C Fahey |
| Journal | International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 10 Issue 9 Pg. 1525-8 (Sep 1984) ISSN: 0360-3016 [Print] United States |
| PMID | 6090355 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.) |
| Chemical References |
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