title: Influence of the cisplatin hydration schedule on topotecan pharmacokinetics.
abstract: The study described here was designed to investigate the influence of the hydration schedule of cisplatin on the pharmacokinetics of topotecan. To test this hypothesis, 13 adult cancer patients were treated with intravenous (i.v.) cisplatin followed by i.v. topotecan for 5 days every 3 weeks using a short hydration schedule (SHS) for cisplatin in the first course and a hyper-hydration schedule (HHS) in the second course or vice versa. Topotecan pharmacokinetic analysis was performed in plasma, whole blood and red blood cells in both courses on days 1, 2 and 5. 11 patients received both courses and were pharmacokinetically evaluable. No significant differences between the two studied schedules were noted in the clearances of topotecan on day 1 in the different matrices. However, in both hydration schedules, on average, slightly lower topotecan clearances were observed on both days 2 and 5 compared with day 1 in all of the matrices, while no differences were noted between days 2 and 5. This alteration was independent of the schedule used and was less pronounced than that which has been initially reported for SHS and, overall, will not have clinical consequences.
authors.affiliation: Department of Medical Oncology, Erasmus MC-Daniel den Hoed Cancer Center, PO Box 5201, 3008 AE Rotterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Gelderblom
authors.forename: W J
authors.initials: WJ
authors.lastname: Loos
authors.forename: A
authors.initials: A
authors.lastname: Sparreboom
authors.forename: O
authors.initials: O
authors.lastname: Soepenberg
authors.forename: M J A
authors.initials: MJ
authors.lastname: de Jonge
authors.forename: D M
authors.initials: DM
authors.lastname: van Boven-van Zomeren
authors.forename: J
authors.initials: J
authors.lastname: Verweij
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D019772:Topotecan / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D019772:Topotecan; D002945:Cisplatin