title: Evaluation of the effect of furosemide on ultrafilterable platinum kinetics in patients treated with cis-diamminedichloroplatinum.
abstract: It has been reported that furosemide can prevent platinum nephrotoxicity by dilution of the toxic drug in the tubule or by another unknown mechanism. To evaluate its influence on ultrafilterable platinum pharmacokinetics, we undertook a randomized prospective trial of cis-diamminedichloroplatinum (CDDP) (80 mg/m2 by a 20-min infusion) administered to 20 patients with hydration-induced diuresis. Ten patients received 20 mg/m2 furosemide 1 h before CDDP administration, and 10 patients received no diuretic drug. Plasma and urinary pharmacokinetics of platinum and creatinine were compared in both groups of patients. Plasma total and ultrafilterable platinum was always higher in the furosemide group. However, protein binding, urinary concentrations, cumulative urinary excretion, renal clearance and creatinine clearance/renal clearance ratio (fractional clearance) were not statistically different. Moreover, the fractional clearance was successively lower, equal and higher than one in both groups. These results suggest that: (1) furosemide probably causes water depletion leading to a rise in plasma concentrations; (2) its protection by a pharmacokinetic interaction is doubtful, since all other parameters (especially urinary parameters) are not significantly modified; (3) renal clearance and fractional clearance suggest a bidirectional transport of platinum in the tubule not influenced by the diuretic drug.
authors.affiliation: Département de Pharmacologie Clinique, Hôpital Général, Dijon, France.
authors.forename: M
authors.initials: M
authors.lastname: Dumas
authors.forename: C
authors.initials: C
authors.lastname: de Gislain
authors.forename: P
authors.initials: P
authors.lastname: d'Athis
authors.forename: V
authors.initials: V
authors.lastname: Chadoint-Noudeau
authors.forename: A
authors.initials: A
authors.lastname: Escousse
authors.forename: J
authors.initials: J
authors.lastname: Guerrin
authors.forename: N
authors.initials: N
authors.lastname: Autissier
mesh_terms: D002945:Cisplatin / Q000493:pharmacokinetics* / Q000633:toxicity; D005665:Furosemide / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008657:Metabolic Clearance Rate; D010984:Platinum / Q000493:pharmacokinetics*; D014462:Ultrafiltration
chemical_list: D010984:Platinum; D005665:Furosemide; D002945:Cisplatin