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Preliminary observations of intraperitoneal carboplatin pharmacokinetics during a phase I study of the Northern California Oncology Group

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  • Carboplatin, Pharmacokinetics
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Summary

The pharmacokinetic behavior of carboplatin administered by the i.p. route at a dose of 200 mg/m2 was studied during five courses of therapy in four patients with ovarian cancer. A regional pharmacologic advantage was noted with carboplatin administered by this route, with (1) peak peritoneal fluid concentrations 18-fold those in plasma, and (2) area under the curve (AUC) for the peritoneum showing a 18-fold and 6-fold increase over plasma AUC at 4 and 24 h, respectively. The mean residence time of total platinum in the peritoneum was 4.7 h. Approximately 10% and 40% of plasma platinum was protein bound at 4 and 24 h after treatment, respectively, whereas peritoneal fluid platinum showed minimal protein binding. Peak plasma platinum levels were comparable to those recorded in previous studies with i.v. doses of carboplatin. Peritoneal clearance of carboplatin in these four patients appeared to be less than that previously reported for cisplatin. Further studies are in progress with higher doses of i.p. carboplatin.

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References

  1. Chiou WL (1978) Critical evaluation of the potential error in pharmacokinetic studies the linear trapezoidal rule method for the calculation of area under the plasma level time curve. J Pharmacokinet Biopharm 6 539–546

    Google Scholar 

  2. Evans BD, Rajus KS, Calvert AH, Harland SJ, Wiltshaw E (1983) Phase II study of JM8, a new platinum analog, advanced ovarian carcinoma. Cancer Treat Rep 67: 997–1000

    Google Scholar 

  3. Gibaldi M, Perrier D (1982) Pharmacokinetics, 2nd edn. Dekker, New York, pp 409–417

    Google Scholar 

  4. Harland SJ, Newell DR, Siddik ZH, Charwick R, Calvert AH, Harrap KR (1984) Pharmacokinetics of cis-diammine-1, 1-cyclobutane dicarboxylate platinum (II) in patients with normal and impaired renal function. Cancer Res 44 1693–1697

    Google Scholar 

  5. Howell SB, Pfeiffle CL, Wung WE, Olshen RA, Lucus WE, Yon JL, Green M (1982) Intraperitoneal cisplatin with thiosulfate protection. Ann Intern Med 97 845–851

    Google Scholar 

  6. Howell SB, Pfeiffle CE, Ohlsen RA (1984) Intraperitoneal chemotherapy with melphalan. Ann Intern Med 101 14–18

    Google Scholar 

  7. Jones RB, Collins JM, Myers CE, Brooks AE, Hubbard SM, Balow JE, Brennen MF, Dedrick RL, DeVita VT (1981) Highvolume intraperitoneal chemotherapy with methotrexate in patients with cancer. Cancer Res 41 55–59

    Google Scholar 

  8. King ME, Pfeiffle CE, Howell SB (1984) Intraperitoneal cytosine arabinoside therapy in ovarian carcinoma. J Clin Oncol 2: 662–669

    Google Scholar 

  9. Lee FH, Canetta R, Issell BF, Lenaz L (1983) New platinum complexes in clinical trials. Cancer Treat Rev 10: 39–51

    Google Scholar 

  10. McVie JG, ten Bokkel Huinink W, Dubbelman R, Franklin H, van der Vijgh W, Klein I (1985) Phase I study and pharmacokinetics of intraperitoneal carboplatin. Cancer Treat Rev 12 [Suppl A] 35–41

    Google Scholar 

  11. Ozols RF, Young RC, Speyer JL, Sugarbaker PH, Greene R, Jenkins J, Meyers CE (1982) Phase I and pharmacological studies of adriamycin administered intraperitoneally to patients with ovarian cancer. Cancer Res 42 4265–4269

    Google Scholar 

  12. Riegelman S, Collier P (1980) The application of statistical moment theory to the evaluation of in vivo dissolution time and absorption time. J Pharm Sci 65 509–535

    Google Scholar 

  13. Sedman AJ, Wagner JG (1976) CSTRIP, a Fortran IV computer program for obtaining initial polyexponential parameter estimates. J Pharm Sci 65 1006–1009

    Google Scholar 

  14. Sharma H, Thatcher N, Baer J, Zaki A, Smith A, McAucliffe CA, Crowther D, Owens S, Fox BW (1983) Blood clearance of radioactively labelled cisdiammine 1, 1-cyclobutane dicarboxylate platinum (II) (CBDCA) in cancer patients. Cancer Chemother Pharmacol 11 5–7

    Google Scholar 

  15. Speyer JL, Collins JM, Dedrick RL, Brennan MF, Buckpitt AR, Londer H, DeVita VT, Myers CE (1980) Phase I and pharmacological studies of 5-flourouracil administered intraperitoneally. Cancer Res 40 567–572

    Google Scholar 

  16. Van Echo DA, Egorin MJ, Whitacre MY, Olman EA, Aisner J (1984) Phase I clinical and pharmacologic trial of carboplatin daily for 5 days. Cancer Treat Rep 68 1103–1114

    Google Scholar 

  17. Vermorken JB, van der Vijgh WJF, Klein I, Hart AAM, Gall HE, Pinefo HM (1984) Pharmacokinetics of free and total platinum species after short-term infusion of cisplatin. Cancer Treat Rep 68 505–513

    Google Scholar 

  18. Yeh KC, Kwan KC (1978) A comparison of numerical integrating algorithms by trapezoidal, lagrange, and spline approximation. J Pharmacokinet Biopharm 6 79–98

    Google Scholar 

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Supported in part by the Louis R. Lurie Foundation, the Randy Lynn Baruh Research Foundation, and grants CA21744, CA19408, CA25827, and CA25862 from the National Institutes of Health, Department of Health and Human Services

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DeGregorio, M.W., Lum, B.L., Holleran, W.M. et al. Preliminary observations of intraperitoneal carboplatin pharmacokinetics during a phase I study of the Northern California Oncology Group. Cancer Chemother. Pharmacol. 18, 235–238 (1986). https://doi.org/10.1007/BF00273393

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  • DOI: https://doi.org/10.1007/BF00273393

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