Abstract
The pharmacokinetics of platinum was investigated in 10 cancer patients treated with a 1-hr infusion of 300 mg/m2 of carboplatin which was given 2–4 days after the administration of 100 mg/kg (20-mg/kg bolus and 80-mg/kg intravenous infusion) of methotrexate. Platinum was analyzed in the samples by flameless atomic absorption spectrophotometry. The concentration vs time data for total platinum in plasma followed a two-compartment model and the mean (and SE) values for β, TBC, V c, and RC were 0.0827 (0.22) hr−1, 2.355 (0.252) liters/hr · m2, 10.74 (0.62) liters/m2, and 2.405 (0.228) liters/hr · m2, respectively. There was no significant change in the creatinine clearance or TBC with repeated treatment. The ultrafilterable platinum which was measured in the plasma of two patients constituted 82 and 11.3% of the total platinum at 1 and 24 hr, respectively, and the data conformed to the one-compartment model. The mean (SE) values for t β, TBC, and V d for free platinum were 1.844 (0.208) hr, 4.583 (1.059) liters/hr · m2, and 11.88 (1.45) liters/m2, respectively. The above data are in good agreement with those reported earlier for platinum following the administration of carboplatin as a single agent. These results suggest that high-dose methotrexate therapy, when administered 2–4 days before carboplatin, does not affect the pharmacokinetics of platinum in the plasma.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
B. D. Evans, K. S. Raju, A. H. Calvert, S. J. Harland, and E. Wiltshaw. Cancer Treat. Rep. 67:997–1000 (1983).
R. F. Ozols, B. C. Behrens, Y. Ostchega, and R. C. Young. Cancer Treat. Rev. 12 (Suppl. A):59–66 (1985).
M. J. Peckham, A. Horwich, M. Brada, A. Drury, and W. F. Hendry. Cancer Treat. Rev. 12 (Suppl. A):101–110 (1985).
R. Canetta, M. Rozencqeig, and S. K. Carter. Cancer Treat. Rev. 12 (Suppl. A):125–136 (1985).
M. E. Gore, A. H. Calvert, and I. E. Smith. Eur. J. Cancer Clin. Oncol. 23:1391–1397 (1987).
I. E. Smith and B. D. Evans. Cancer Treat. Rev. 12 (Suppl. A):73–75 (1985).
J. M. Koeller, D. L. Trump, K. D. Tutsch, R. H. Earhart, T. E. Davis, and D. C. Tormey. Cancer 57:222–225 (1986).
D. A. Van Echo, M. J. Egorin, M. Y. Whitacre, E. A. Olman, and J. Aisner. Cancer Treat. Rep. 68:1103–1114 (1984).
G. A. Curt, J. J. Grygiel, B. J. Corden, R. F. Ozols, R. B. Weiss, D. T. Tell, C. E. Meyers, and J. M. Collins. Cancer Res. 43:4470–4473 (1983).
S. J. Harland, D. R. Newell, Z. H. Siddik, R. Chadwick, A. H. Calvert, and K. R. Harrap. Cancer Res. 44:1693–1697 (1984).
D. W. DeGregorio, B. L. Lum, W. M. Holleran, B. J. Wilbur, and B. I. Sikic. Cancer Chemother. Pharmacol. 18:235–238 (1986).
J. G. McVie, W. ten Bokkel Huinink, R. Dubbelman, H. Franklin, W. van der Vijgh, and I. Klein. Cancer Treat. Rev. 12 (Suppl. A):35–41 (1985).
W. ten Bokkel Huinink, M. E. L. van der Burg, J. B. Vermorken, and A. van Oosterom. Proc. Eur. Conf. Clin. Oncol. 3:177 (1985) (abstr.).
J. Wagstaff and D. Crowther. Proc. Eur. Conf. Clin. Oncol. 3:119 (1985) (abstr.).
R. Rosso, P. F. Conte, M. Bruzzone, S. Chiara, G. Giaccone, E. Materman, and C. R. Franks. Proc. Eur. Conf. Clin. Oncol. 3:115 (1985) (abstr.).
B. A. Chabner, C. E. Myers, and V. T. Oliverio. Semin. Oncol. 4:165–191 (1977).
A. El-Yazigi and I. Al-Saleh. Ther. Drug Monit. 8:318–320 (1986).
M. Gibaldi and D. Perrier. Pharmacokinetics, Marcel Dekker, New York, 1975.
D. J. Dixon (ed.), BMDP Statistical Software, University of California Press, Berkeley, 1983.
L. Lenaz. Paraplatin (Carboplatin) Compendium of Recent Data, Bristol-Meyers International Group, New York, 1986.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
El-Yazigi, A., Amer, M. & Martin, C.R. Pharmacokinetics of Platinum in Cancer Patients Treated with Carboplatin in Combination with High-Dose Methotrexate. Pharm Res 6, 492–496 (1989). https://doi.org/10.1023/A:1015920524065
Issue Date:
DOI: https://doi.org/10.1023/A:1015920524065