The disposition of carboplatin in ovarian cancer patients

Robert C. Gaver, Nicoletta Colombo, Michael D. Green, Alice M. George, George Deeb, Alan D. Morris, Renzo M. Canetta, James L. Speyer, Raymond H. Farmen, Franco M. Muggia

Research output: Contribution to journalArticle

Abstract

Carboplatin was given as a 30-min infusion to 11 ovarian cancer patients at doses of 170-500 mg/m2. The ages, weights, and creatinine clearances (Clcr) ranged from 44 to 75 years, from 44 to 74 kg, and from 32 to 101 ml/min, respectively. Plasma, plasma ultrafiltrate (PU), and urine samples were obtained at appropriate times for 96 h and were analyzed for platinum. The PU and urine were also analyzed for the parent compound by HPLC. In patients with a Clcr of about 60 ml/min or greater, carboplatin decayed biexponentially with a mean t1/2α of 1.6 h and a t1/2β of 3.0 h. The mean (±SD) residence time, total body clearance, and apparent volume of distribution were 3.5±0.4 h, 4.4±0.85 l/h, and 16±31l, respectively. Cmax and AUCinf values increased linearly with dose, and the latter values correlated better with the dose in mg than in mg/m2. No significant quantities of free, ultrafilterable, platinum-containing species other than the parent compound were found in plasma, but platinum from carboplatin became protein-bound and was slowly eliminated with a minimal t1/2 of 5 days. The major route of elimination was excretion via the kidneys. Patients with a Clcr of 60 ml/min or greater excreted 70% of the dose as the parent compound in the urine, with most of this occurring within 12-16 h. All of the platinum in 24-h urine was carboplatin, and only 2%-3% of the dosed platinum was excreted from 48 to 96 h. Patients with a Clcr of less than about 60 ml/min exhibited dose-disproportional increases in AUCinf and MRT values. The latter were inversely related to Clcr (r=-0.98). Over a dose range of 300-500 mg/m2, carboplatin exhibited linear, dose-independent pharmaco-kinetics in patients with a Clcr of about 60 ml/min or greater, but dose reductions are necessary for patients with mild renal failure.

Original languageEnglish
Pages (from-to)263-270
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume22
Issue number3
DOIs
Publication statusPublished - Sep 1988

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Carboplatin
Platinum
Ovarian Neoplasms
Plasmas
Urine
Pharmacokinetics
Creatinine
Renal Insufficiency
High Pressure Liquid Chromatography
Kidney
Weights and Measures
Proteins

ASJC Scopus subject areas

  • Pharmacology
  • Oncology
  • Cancer Research

Cite this

Gaver, R. C., Colombo, N., Green, M. D., George, A. M., Deeb, G., Morris, A. D., ... Muggia, F. M. (1988). The disposition of carboplatin in ovarian cancer patients. Cancer Chemotherapy and Pharmacology, 22(3), 263-270. https://doi.org/10.1007/BF00273422

The disposition of carboplatin in ovarian cancer patients. / Gaver, Robert C.; Colombo, Nicoletta; Green, Michael D.; George, Alice M.; Deeb, George; Morris, Alan D.; Canetta, Renzo M.; Speyer, James L.; Farmen, Raymond H.; Muggia, Franco M.

In: Cancer Chemotherapy and Pharmacology, Vol. 22, No. 3, 09.1988, p. 263-270.

Research output: Contribution to journalArticle

Gaver, RC, Colombo, N, Green, MD, George, AM, Deeb, G, Morris, AD, Canetta, RM, Speyer, JL, Farmen, RH & Muggia, FM 1988, 'The disposition of carboplatin in ovarian cancer patients', Cancer Chemotherapy and Pharmacology, vol. 22, no. 3, pp. 263-270. https://doi.org/10.1007/BF00273422
Gaver, Robert C. ; Colombo, Nicoletta ; Green, Michael D. ; George, Alice M. ; Deeb, George ; Morris, Alan D. ; Canetta, Renzo M. ; Speyer, James L. ; Farmen, Raymond H. ; Muggia, Franco M. / The disposition of carboplatin in ovarian cancer patients. In: Cancer Chemotherapy and Pharmacology. 1988 ; Vol. 22, No. 3. pp. 263-270.
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abstract = "Carboplatin was given as a 30-min infusion to 11 ovarian cancer patients at doses of 170-500 mg/m2. The ages, weights, and creatinine clearances (Clcr) ranged from 44 to 75 years, from 44 to 74 kg, and from 32 to 101 ml/min, respectively. Plasma, plasma ultrafiltrate (PU), and urine samples were obtained at appropriate times for 96 h and were analyzed for platinum. The PU and urine were also analyzed for the parent compound by HPLC. In patients with a Clcr of about 60 ml/min or greater, carboplatin decayed biexponentially with a mean t1/2α of 1.6 h and a t1/2β of 3.0 h. The mean (±SD) residence time, total body clearance, and apparent volume of distribution were 3.5±0.4 h, 4.4±0.85 l/h, and 16±31l, respectively. Cmax and AUCinf values increased linearly with dose, and the latter values correlated better with the dose in mg than in mg/m2. No significant quantities of free, ultrafilterable, platinum-containing species other than the parent compound were found in plasma, but platinum from carboplatin became protein-bound and was slowly eliminated with a minimal t1/2 of 5 days. The major route of elimination was excretion via the kidneys. Patients with a Clcr of 60 ml/min or greater excreted 70{\%} of the dose as the parent compound in the urine, with most of this occurring within 12-16 h. All of the platinum in 24-h urine was carboplatin, and only 2{\%}-3{\%} of the dosed platinum was excreted from 48 to 96 h. Patients with a Clcr of less than about 60 ml/min exhibited dose-disproportional increases in AUCinf and MRT values. The latter were inversely related to Clcr (r=-0.98). Over a dose range of 300-500 mg/m2, carboplatin exhibited linear, dose-independent pharmaco-kinetics in patients with a Clcr of about 60 ml/min or greater, but dose reductions are necessary for patients with mild renal failure.",
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N2 - Carboplatin was given as a 30-min infusion to 11 ovarian cancer patients at doses of 170-500 mg/m2. The ages, weights, and creatinine clearances (Clcr) ranged from 44 to 75 years, from 44 to 74 kg, and from 32 to 101 ml/min, respectively. Plasma, plasma ultrafiltrate (PU), and urine samples were obtained at appropriate times for 96 h and were analyzed for platinum. The PU and urine were also analyzed for the parent compound by HPLC. In patients with a Clcr of about 60 ml/min or greater, carboplatin decayed biexponentially with a mean t1/2α of 1.6 h and a t1/2β of 3.0 h. The mean (±SD) residence time, total body clearance, and apparent volume of distribution were 3.5±0.4 h, 4.4±0.85 l/h, and 16±31l, respectively. Cmax and AUCinf values increased linearly with dose, and the latter values correlated better with the dose in mg than in mg/m2. No significant quantities of free, ultrafilterable, platinum-containing species other than the parent compound were found in plasma, but platinum from carboplatin became protein-bound and was slowly eliminated with a minimal t1/2 of 5 days. The major route of elimination was excretion via the kidneys. Patients with a Clcr of 60 ml/min or greater excreted 70% of the dose as the parent compound in the urine, with most of this occurring within 12-16 h. All of the platinum in 24-h urine was carboplatin, and only 2%-3% of the dosed platinum was excreted from 48 to 96 h. Patients with a Clcr of less than about 60 ml/min exhibited dose-disproportional increases in AUCinf and MRT values. The latter were inversely related to Clcr (r=-0.98). Over a dose range of 300-500 mg/m2, carboplatin exhibited linear, dose-independent pharmaco-kinetics in patients with a Clcr of about 60 ml/min or greater, but dose reductions are necessary for patients with mild renal failure.

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