Disposition of total and free cisplatin on two consecutive treatment cycles in patients with ovarian cancer

Charles Erlichman, Steven J. Soldin, Jake J. Thiessen, F. G. Sturgeon, Sheldon Fine

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The disposition of total and ultrafilterable cisplatin was determined in 12 women with ovarian carcinoma receiving cyclophosphamide 500 mg/m2, adriamycin 50 mg/m2 and cisplatin 50 mg/m2 during their first and second course. Plasma samples were obtained over 96 h following the completion of the cisplatin infusion and assayed for total platinum by atomic absorption spectroscopy. Plasma samples obtained up to 4 h after cisplatin infusion contained measurable ultrafilterable (free) cisplatin. The mean disposition of free cisplatin conformed to a two-compartment model with a mean terminal half-life (±SD) of 46.2±20.2 min during the first course and 37.8±18.0 min during the second course of therapy. The mean disposition of total cisplatin conformed to a three-compartment model with a mean terminal half-life (±SD) of 57.8±19.3 h during the first course and 86.6±33.3 h during the second course of therapy. We found that the mean total cisplatin levels were significantly higher during the second course than the first course and the total body clearance of total platinum decreased from the first to the second course. Divided urine collections were obtained over 24 h after completion of cisplatin infusion, but cisplatin was not always detectable at all time intervals. The total fraction recovered was 0.14 and 0.12 of administered dose after the first and the second course, respectively. Renal clearance was 0.61±0.32 l/h/m2 and 0.45±0.16 l/h/m2 for the first and the second course, respectively. We conclude that: (1) urinary platinum excretion is variable between patients and with time; (2) a trend to decreased renal clearance of platinum from first to second course may be due to a decrease in renal excretion of cisplatin; and (3) the body's elimination pathways clear less platinum upon repeat administration.

Original languageEnglish (US)
Pages (from-to)75-79
Number of pages5
JournalCancer Chemotherapy and Pharmacology
Volume19
Issue number1
DOIs
StatePublished - Feb 1987
Externally publishedYes

Fingerprint

Ovarian Neoplasms
Cisplatin
Platinum
Therapeutics
Half-Life
Kidney
Plasmas
Atomic spectroscopy
Urine Specimen Collection
Absorption spectroscopy
Doxorubicin
Cyclophosphamide
Spectrum Analysis
Carcinoma

ASJC Scopus subject areas

  • Pharmacology
  • Oncology
  • Cancer Research

Cite this

Disposition of total and free cisplatin on two consecutive treatment cycles in patients with ovarian cancer. / Erlichman, Charles; Soldin, Steven J.; Thiessen, Jake J.; Sturgeon, F. G.; Fine, Sheldon.

In: Cancer Chemotherapy and Pharmacology, Vol. 19, No. 1, 02.1987, p. 75-79.

Research output: Contribution to journalArticle

Erlichman, Charles ; Soldin, Steven J. ; Thiessen, Jake J. ; Sturgeon, F. G. ; Fine, Sheldon. / Disposition of total and free cisplatin on two consecutive treatment cycles in patients with ovarian cancer. In: Cancer Chemotherapy and Pharmacology. 1987 ; Vol. 19, No. 1. pp. 75-79.
@article{69a5ba8d0d824c6bbf3ba911569c4a21,
title = "Disposition of total and free cisplatin on two consecutive treatment cycles in patients with ovarian cancer",
abstract = "The disposition of total and ultrafilterable cisplatin was determined in 12 women with ovarian carcinoma receiving cyclophosphamide 500 mg/m2, adriamycin 50 mg/m2 and cisplatin 50 mg/m2 during their first and second course. Plasma samples were obtained over 96 h following the completion of the cisplatin infusion and assayed for total platinum by atomic absorption spectroscopy. Plasma samples obtained up to 4 h after cisplatin infusion contained measurable ultrafilterable (free) cisplatin. The mean disposition of free cisplatin conformed to a two-compartment model with a mean terminal half-life (±SD) of 46.2±20.2 min during the first course and 37.8±18.0 min during the second course of therapy. The mean disposition of total cisplatin conformed to a three-compartment model with a mean terminal half-life (±SD) of 57.8±19.3 h during the first course and 86.6±33.3 h during the second course of therapy. We found that the mean total cisplatin levels were significantly higher during the second course than the first course and the total body clearance of total platinum decreased from the first to the second course. Divided urine collections were obtained over 24 h after completion of cisplatin infusion, but cisplatin was not always detectable at all time intervals. The total fraction recovered was 0.14 and 0.12 of administered dose after the first and the second course, respectively. Renal clearance was 0.61±0.32 l/h/m2 and 0.45±0.16 l/h/m2 for the first and the second course, respectively. We conclude that: (1) urinary platinum excretion is variable between patients and with time; (2) a trend to decreased renal clearance of platinum from first to second course may be due to a decrease in renal excretion of cisplatin; and (3) the body's elimination pathways clear less platinum upon repeat administration.",
author = "Charles Erlichman and Soldin, {Steven J.} and Thiessen, {Jake J.} and Sturgeon, {F. G.} and Sheldon Fine",
year = "1987",
month = "2",
doi = "10.1007/BF00296261",
language = "English (US)",
volume = "19",
pages = "75--79",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",
number = "1",

}

TY - JOUR

T1 - Disposition of total and free cisplatin on two consecutive treatment cycles in patients with ovarian cancer

AU - Erlichman, Charles

AU - Soldin, Steven J.

AU - Thiessen, Jake J.

AU - Sturgeon, F. G.

AU - Fine, Sheldon

PY - 1987/2

Y1 - 1987/2

N2 - The disposition of total and ultrafilterable cisplatin was determined in 12 women with ovarian carcinoma receiving cyclophosphamide 500 mg/m2, adriamycin 50 mg/m2 and cisplatin 50 mg/m2 during their first and second course. Plasma samples were obtained over 96 h following the completion of the cisplatin infusion and assayed for total platinum by atomic absorption spectroscopy. Plasma samples obtained up to 4 h after cisplatin infusion contained measurable ultrafilterable (free) cisplatin. The mean disposition of free cisplatin conformed to a two-compartment model with a mean terminal half-life (±SD) of 46.2±20.2 min during the first course and 37.8±18.0 min during the second course of therapy. The mean disposition of total cisplatin conformed to a three-compartment model with a mean terminal half-life (±SD) of 57.8±19.3 h during the first course and 86.6±33.3 h during the second course of therapy. We found that the mean total cisplatin levels were significantly higher during the second course than the first course and the total body clearance of total platinum decreased from the first to the second course. Divided urine collections were obtained over 24 h after completion of cisplatin infusion, but cisplatin was not always detectable at all time intervals. The total fraction recovered was 0.14 and 0.12 of administered dose after the first and the second course, respectively. Renal clearance was 0.61±0.32 l/h/m2 and 0.45±0.16 l/h/m2 for the first and the second course, respectively. We conclude that: (1) urinary platinum excretion is variable between patients and with time; (2) a trend to decreased renal clearance of platinum from first to second course may be due to a decrease in renal excretion of cisplatin; and (3) the body's elimination pathways clear less platinum upon repeat administration.

AB - The disposition of total and ultrafilterable cisplatin was determined in 12 women with ovarian carcinoma receiving cyclophosphamide 500 mg/m2, adriamycin 50 mg/m2 and cisplatin 50 mg/m2 during their first and second course. Plasma samples were obtained over 96 h following the completion of the cisplatin infusion and assayed for total platinum by atomic absorption spectroscopy. Plasma samples obtained up to 4 h after cisplatin infusion contained measurable ultrafilterable (free) cisplatin. The mean disposition of free cisplatin conformed to a two-compartment model with a mean terminal half-life (±SD) of 46.2±20.2 min during the first course and 37.8±18.0 min during the second course of therapy. The mean disposition of total cisplatin conformed to a three-compartment model with a mean terminal half-life (±SD) of 57.8±19.3 h during the first course and 86.6±33.3 h during the second course of therapy. We found that the mean total cisplatin levels were significantly higher during the second course than the first course and the total body clearance of total platinum decreased from the first to the second course. Divided urine collections were obtained over 24 h after completion of cisplatin infusion, but cisplatin was not always detectable at all time intervals. The total fraction recovered was 0.14 and 0.12 of administered dose after the first and the second course, respectively. Renal clearance was 0.61±0.32 l/h/m2 and 0.45±0.16 l/h/m2 for the first and the second course, respectively. We conclude that: (1) urinary platinum excretion is variable between patients and with time; (2) a trend to decreased renal clearance of platinum from first to second course may be due to a decrease in renal excretion of cisplatin; and (3) the body's elimination pathways clear less platinum upon repeat administration.

UR - http://www.scopus.com/inward/record.url?scp=0023137206&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023137206&partnerID=8YFLogxK

U2 - 10.1007/BF00296261

DO - 10.1007/BF00296261

M3 - Article

C2 - 3815729

AN - SCOPUS:0023137206

VL - 19

SP - 75

EP - 79

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 1

ER -