A comparative study of the distribution in the male rat of platinum-labelled cis-dichlorodiammine platinum (II), cis-trans-dichlorodihydroxy-bis-(isopropylamine) platinum (I), and cis-dichloro-bis-cyclopropylamine platinum (II) |
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| Authors: | R. Harrison C. A. McAuliffe A. Zaki J. Baer H. Sharma A. Smith H. Jackson B. W. Fox |
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| Affiliation: | (1) Inorganic Chemistry, University of Manchester Institute of Science and Technology, Oxford Rd, M 13 9PL Manchester;(2) Medical Biophysics, University of Manchester Medical School, Oxford Rd, M 13 9PL Manchester;(3) Pharmacology, Medical School, University of Manchester, Oxford Rd, M 13 9PL Manchester;(4) Paterson Laboratories, Christie Hospital, Wilmslow Road, Withington, M 20 9BX Manchester, England;(5) Holt Radium Institute, Wilmslow Road, Withington, M 20 9BX Manchester, England |
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| Abstract: | Summary Three platinum derivatives, cis-dichlorodiammine platinum (II), (DDP), cis-trans-dichlorodihydroxy-bis-(isopropylamine)platinum (IV) (CHIP) and cis-dichloro-bis-cyclopropylamine platinum (II) (CP), have been prepared with a gamma-emitting platinum label. The distribution of these complexes was studied in male rats.The results are presented as fractions of the administered radiolabel per gram of tissue and per total organ. Accumulation in the liver was highest initially following CP and lowest after DDP, but by 14 days the levels in kidney and liver were highest with CP. The concentration in the skin was relatively high after all the compounds, but was the most conspicuous after DDP at the early times. In general, patterns of distribution between the other organs were similar with DDP and CP.CHIP, however, exhibited a different pattern of distribution. Over the first 24 h the level of platinum in most tissues declined more rapidly than after either of the other two compounds but the residual label persisted for a longer period. In the kidney there appeared to be a secondary uptake of labelled material, presumably from other tissues. The level present at 14 days after CHIP was also significantly higher in a number of other organs than after the other two drugs. The increase in label in the spleen at the later times may be due to the removal of circulating damaged cells and consistent with the higher levels of residual platinum in the blood. There was also a higher level of residual platinum in the blood especially after IV administration of the labelled agent.The results show that CHIP was cleared at a faster rate from blood and kidney than the other two complexes, results which closely resembled clinical findings with these three agents, to be published elsewhere.The greater retention time of label after CHIP also suggests that longer-term toxicity may follow its repeated administration.Present address: Radiochemical Centre, Amersham International |
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