Coadministration of oxaliplatin does not influence the pharmacokinetics of gemcitabine (Journal article)

Pappas, P./ Mavroudis, D./ Nikolaidou, M./ Georgoulias, V./ Marselos, M.

We investigated the possible pharmacokinetic interactions of gemcitabine and oxaliplatin in patients with advanced solid tumors. Ten patients with advanced stage solid tumors were treated with gemcitabine (1500 mg/m) as a 30-min intravenous infusion on days 1 and 8, followed by oxaliplatin (130 mg/m) as a 4-h intravenous infusion, on day 8 every 21 days. Pharmacokinetic data for 24 h after dosing were obtained for both day 1 (gemcitabine without oxaliplatin coadministration) and day 8 (gemcitabine with oxaliplatin) during the first cycle of treatment. Gemcitabine levels in plasma were quantified using a reverse-phase high-performance liquid chromatography assay with ultraviolet detection, and total and ultrafiltrated platinum levels by flameless atomic absorption spectrophotometry with deuterium correction. All pharmacokinetic parameters of gemcitabine seemed to be unchanged when coadministered with oxaliplatin (day 8) compared with pharmacokinetic data of gemcitabine given as a single agent (day 1). The mean (maximum) concentration of gemcitabine on days 1 and 8 was 13.57 (+/-7.42) and 10.23 (+/-5.21) mg/l, respectively (P=0.28), and the mean half-life was 0.32 and 0.44 h, respectively (P=0.40). Similarly, the P-values for AUC0-24 and the observed clearance were 0.61 and 0.30, respectively. Plasma total and free platinum levels were in agreement with other published data. Gemcitabine disposition appeared to be unaffected by oxaliplatin coadministration because no significant changes in pharmacokinetics between day 1 (gemcitabine without oxaliplatin coadministration) and day 8 (gemcitabine with oxaliplatin) were observed.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: Adolescent,Adult,Aged,Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse,effects,Area Under Curve,Deoxycytidine/administration & dosage/adverse effects/*analogs &,derivatives/pharmacokinetics,Drug Interactions,Female,Humans,Male,Middle Aged,Neoplasms/drug therapy,Organoplatinum Compounds/*administration & dosage/adverse effects,Platinum/blood/pharmacokinetics,Treatment Outcome
ISSN: 0959-4973
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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