Pharmacokinetics of carboplatin after i.v. administration.

F. Elferink, W. J. van der Vijgh, I. Klein, J. B. Vermorken, H. E. Gall, H. M. Pinedo

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1231-1237
Number of pages7
JournalCancer Treatment Reports
Volume71
Issue number12
StatePublished - Dec 1987
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Elferink, F., van der Vijgh, W. J., Klein, I., Vermorken, J. B., Gall, H. E., & Pinedo, H. M. (1987). Pharmacokinetics of carboplatin after i.v. administration. Cancer Treatment Reports, 71(12), 1231-1237.