Amifostine (Ethyol) administered to cancer patients is rapidly cleared from 
plasma by a biphasic decay with an alpha half-life (T1/2 alpha) of 0.88 min and 
a T1/2 beta of 8.8 min. The result is that more than 90% of the drug has 
disappeared from the plasma compartment 6 min after intravenous (i.v.) 
administration. Only approximately 1% of the dose appears in the ascites. Animal 
studies indicate that amifostine is primarily excreted in urine-approximately 6% 
of the dose is excreted in the urine as amifostine and its metabolites WR-1065 
and disulphides-which means that a large percentage of the dose is taken up by 
the tissues. Maximal tissue concentrations of WR-1065 and the disulphides were 
obtained between 10 and 30 min after an intraperitoneal injection of amifostine 
in mice, with the lowest concentrations in tumour tissues. Because WR-1065 gives 
protection to normal tissues rather than rescue, the pharmacokinetic data 
indicate that amifostine must be given shortly before administration of the 
cytostatic drug or radiation from which protection is required. For these 
reasons, amifostine is given to patients as a 15-min i.v. infusion before 
cisplatin and carboplatin to protect against their dose-limiting toxicities. In 
some regimens carboplatin is combined with three doses of amifostine because of 
the high concentration of the active carboplatin species during the first 4 h 
after administration. When carboplatin was administered as a 15-min i.v. 
infusion of 400 mg/m2 and amifostine as a 15-min i.v. infusion of 740 mg/m2 just 
before and 2 and 4 h after carboplatin, the area under the plasma 
concentration-time curve for ultrafilterable platinum increased from 253 +/- 45 
microM.h (n = 6) for carboplatin alone to 305 +/- 63 microM.h (n = 11) for 
carboplatin+three doses of amifostine. Experiments in nude mice bearing OVCAR-3 
xenografts showed that amifostine, given once before cisplatin or three times in 
combination with carboplatin, did not affect the antitumour effect of these 
drugs. When amifostine was only given just before carboplatin, it even 
stimulated the antitumour effect of carboplatin significantly.