Pharmacokinetics of amifostine and its metabolites in the plasma and ascites of a cancer patient

• Published in: Cancer chemotherapy and pharmacology Vol. 39; no. 1-2; pp. 162 - 166
• Main Authors: KORST, A. E. C, GALL, H. E, VERMORKEN, J. B, VAN DER VIJGH, W. J. F
• Format: Journal Article
• Language: English
• Published: Berlin Springer 1996
• Subjects: Adenocarcinoma - metabolism; Amifostine - metabolism; Amifostine - pharmacokinetics; Ascites - metabolism; Biological and medical sciences; Chromatography, High Pressure Liquid; Disulfides - blood; Drug toxicity and drugs side effects treatment; Half-Life; Humans; Infusions, Intravenous; Male; Medical sciences; Mercaptoethylamines - pharmacokinetics; Middle Aged; Miscellaneous (drug allergy, mutagens, teratogens...); Pharmacology. Drug treatments; Radiation-Protective Agents - metabolism; Radiation-Protective Agents - pharmacokinetics; Stomach Neoplasms - metabolism; Adenocarcinoma; Antineoplastic agent; Human; Stomach; Drug combination; Intravenous administration; Metabolite; Toxicity; Malignant tumor; Amifostine; Blood plasma; Prevention; Chemotherapy; Organic disulfide; Treatment; Carboplatin; Digestive diseases; Ascites; Pharmacokinetics; Gastric disease; Platinum II Complexes
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s002800050553

The pharmacokinetics of amifostine, a protector against chemotherapy and radiation-induced toxicities, was investigated in the plasma and ascites of a cancer patient. A high-performance liquid chromatography (HPLC) procedure with electrochemical detection was used to measure amifostine, its active metabolite, WR 1065, and the disulfides (symmetrical plus mixed disulfides). Both amifostine and WR 1065 were rapidly cleared from the plasma (95% and 50% of the peak concentration within 1 h, respectively). The disulfides, which were rapidly formed from WR 1065, were cleared much more slowly (final half-life 13.6 h). Multiple dosing resulted in a tendency toward increasing peak levels of WR 1065 and decreasing peak levels of the disulfides. Only 1% of the delivered dose appeared in the ascites. Therefore, it is not plausible that the presence of ascites or other third spaces would have an impact on the pharmacokinetics of amifostine.