title: Pharmacokinetics of carboplatin after i.v. administration.
abstract: Pharmacokinetics of the cisplatin analog carboplatin were studied in ovarian cancer patients who received short-term iv infusions of 290-370 mg/m2. Platinum (Pt) was determined by atomic absorption spectrometry in plasma ultrafiltrate up to 24 hours and in plasma and urine up to 5 days following infusion. Carboplatin was determined in plasma ultrafiltrate and in urine by high-performance liquid chromatography with electrochemical detection. The final half-life of total Pt in plasma was 5.8 +/- 1.6 days. Pharmacokinetics of carboplatin and ultrafilterable Pt (free Pt) were similar with respect to alpha-half-life (16 +/- 6 and 23 +/- 8 mins), beta-half-life (118 +/- 15 and 120 +/- 11 mins), area under curve/dose (18 +/- 5 and 17 +/- 4 min/m2/L), total-body clearance (101 +/- 21 and 107 +/- 19 ml/min), and volume of distribution Vss (9.9 +/- 1.3 and 10.0 +/- 1.4 L/m2). After 6 hours the cumulative urinary excretion of carboplatin and Pt was 41% +/- 14% and 68% +/- 7% of the dose, respectively. After 5 days the cumulative urinary excretion of Pt was 84% +/- 6%. Renal and metabolic clearances of free Pt from plasma were 81 +/- 17 and 26 +/- 11 ml/minute, respectively. The first-order rate constant for metabolic elimination of free Pt (KM = CLM/Vss) was 1.5 X 10(-3) +/- 0.6 X 10(-3) min-1, which is ten times lower than the value calculated from literature data for cisplatin (15 X 10(-3) +/- 1 X 10(-3) min-1). This means that the overall in vivo reactivity of carboplatin is ten times lower than that of cisplatin.
authors.affiliation: Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Elferink
authors.forename: W J
authors.initials: WJ
authors.lastname: van der Vijgh
authors.forename: I
authors.initials: I
authors.lastname: Klein
authors.forename: J B
authors.initials: JB
authors.lastname: Vermorken
authors.forename: H E
authors.initials: HE
authors.lastname: Gall
authors.forename: H M
authors.initials: HM
authors.lastname: Pinedo
mesh_terms: D016190:Carboplatin; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D009944:Organoplatinum Compounds / Q000378:metabolism / Q000493:pharmacokinetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010984:Platinum / Q000378:metabolism
chemical_list: D009944:Organoplatinum Compounds; D010984:Platinum; D016190:Carboplatin