Print Email Facebook Twitter Influence of amifostine on the pharmacokinetics of cisplatin in cancer patients Title Influence of amifostine on the pharmacokinetics of cisplatin in cancer patients Author Korst, A.E.C. van der Sterre, M.L.T. Gall, H.E. Fichtinger-Schepman, A.M.J. Vermorken, J.B. van der Vijgh, W.J.F. Centraal Instituut voor Voedingsonderzoek TNO Publication year 1998 Abstract The pharmacokinetics of cisplatin was investigated in 13 patients receiving 18 courses of cisplatin alone or in combination with amifostine to investigate the influence of amifostine (WR 2721; Ethyol) on the pharmacokinetics of cisplatin. Cisplatin was administered as a 1-h i.v. infusion, whereas amifostine was given i.v. over 15 min just before the cisplatin infusion. An increase in the final half-life of ultrafilterable platinum was observed after treatment with cisplatin and amifostine (t( 1/4 ), 0.77 ± 0.10 h; n = 8), compared to cisplatin alone (t( 1/4 ), 0.57 ± 0.15 h; n = 8). This might be caused by an influence of amifostine on the kidney function, because an increase in the serum creatinine levels was also observed 24 h after treatment with cisplatin and amifostine (13.8 ± 12.6%; n = 9), which was not observed after treatment with cisplatin alone (-0.1 ± 6.8%; n = 9). Surprisingly, the final half-life of unchanged cisplatin did not increase, but even showed a slight decrease after treatment with amifostine. In vitro data would suggest that this might be due to a chemical interaction between cisplatin and amifostine. Because the AUC values of ultrafilterable platinum and unchanged cisplatin did not change significantly and no change in Pt-DNA adduct (Pt-GG) levels in leukocytes was observed upon addition of amifostine in the treatment schedule, the change in the pharmacokinetics of cisplatin is most probably of minor importance and has no significant impact on the efficacy of cisplatin, as already confirmed by clinical studies. Subject NutritionAmifostineCisplatinCreatinineAdultAgedArea under the curveClinical articleCreatinine blood levelDna adductDna drug complexDrug blood levelDrug effectDrug half lifeFemaleHumanIntravenous drug administrationKidney functionMaleMalignant neoplastic diseasePriority journalAmifostineAntineoplastic AgentsCisplatinDNA AdductsDrug InteractionsFemaleHalf-LifeHemofiltrationHumansLeukocytesMaleMiddle AgedNeoplasmsPlatinumRadiation-Protective Agents To reference this document use: http://resolver.tudelft.nl/uuid:e845b3f6-004e-43df-88ef-dbd008cbcdf6 TNO identifier 234360 ISSN 1078-0432 Source Clinical Cancer Research, 4 (2), 331-336 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.