Summary
We have studied the disposition of bleomycin, melphalan, or vinblastine after intraperitoneal (IP) instillation in 14 cancer patients. Although IP bleomycin had a somewhat longer terminal-phase plasma half-life than after intravenous (IV) administration (5.5 vs 4.0 h, respectively), its systemic absorption averaged only 44%–52% of the administered dose. IP melphalan’s mean terminal-phase half-life of 1.3 h was similar to that seen after IV drug administration. Melphalan’s systemic absorption from the IP space averaged only 39% of the administered dose. In contrast, vinblastine plasma levels remained elevated for longer than 24 h after IP instillation. Its use was associated with life-threatening adynamic ileus in two patients. Bleomycin’s and melphalan’s reduced systemic availability after IP dosing suggests that their dose could be increased safely by a factor of two over their standard IV doses.
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References
Alberts DS (1979) Pharmakinetics of melphalan in man: intravenous administration. Clin Pharmacol Therap 26:73–80
Alberts DS, (1978) Bleomycin pharmacokinetics in man. I. Intravenous administration. Cancer Chemother Pharmacol 1:177–181
Alberts DS, Chen H-SG, Mayersohn M, Perrior D, Moon TE, Gross JF (1979) Bleomycin pharmacokinetics in man. II. Intracavitary administration. Cancer Chemother Pharmacol 2:127–132
Broughton A, Strong JE (1976) Radioimmunoassay of bleomycin. Cancer Res 36:1418–1421
Chang SY, Alberts DS, Melnick LR, Walson PD, Salmon SE (1978) High-pressure liquid chromatographic analysis of melphalan in plasma. J Pharm Sci 67:679–681
Comis RL (1978) Bleomycin pulmonary toxicity. In: Carter SK, Crooke ST, Umezawa H (eds) Bleomycin: Current status and new developments. Academic Press, New York, pp 279–291
Dedrick RL, Myers CS, Bungay PM, DeVita VT Jr (1978) Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep 62:1–11
Lu K, Yep HY, Watts S, Loo TL (1979) Comparative clinical pharmacology of vinblastine (VBL) in patients with advanced breast cancer: Single versus continuous infusion. Proc Am Assoc Cancer Res and Am Soc Clin Oncol 20: C–333
Metzler CM (1969) NONLIN: A computer program for parameter estimation in nonlinear situations. Upjohn Co., Kalamazoo, Michigan (Technical Rep 7292/69/7292/005)
Myers C, Jones R, Londer H, Hubbard S, Brennan M, Balow J, Dedrick R, Ozols R, DeVita V (1978) Pharmacology of high-dose methotrexate (MTX) administered via peritoneal dialysis. Proc Am Assoc Cancer Res and Am Soc Clin Oncol 19: C–333
Owellen RJ, Hartke CA, Hains FO (1977) Pharmacokinetics and metabolism in vinblastine in humans. Cancer Res 37:2597–2602
Ozols R, Grotzinger K, Myers C, Yong RC (1979) Ovarian cancer (OC): Intraperitoneal (LP.) therapy with adriamycin (ADR). Proc Am Assoc Cancer Res and Am Soc Clin Oncol 20:978
Sedman AJ, Wagner JG (1976) CSTRIP: A Fortran IV computer program for obtaining initial polyexponential parameter estimates. J Pharm Sci 65:1006–1010
Speyer JL, Collins JM, Dedrick RL, Brennan H, Londer H, DeVita VT, Jr, Myers CE (1979) Phase I and pharmacological studies of intraperitoneal (LP.) 5-fluorouracil (5.Fu). Proc Am Assoc Cancer Res and Am Soc Clin Oncol 19: C–333
Tobias JS, Griffiths CF (1976) Management of ovarian carcinoma. Current concepts and future prospects. Part 1. N Engl J Med 294:818–822
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© 1980 Springer-Verlag Berlin Heidelberg
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Alberts, D.S., Chen, HS.G., Chang, S.Y., Peng, Y.M. (1980). The Disposition of Intraperitoneal Bleomycin, Melphalan, and Vinblastine in Cancer Patients. In: Mathé, G., Muggia, F.M. (eds) Cancer Chemo- and Immunopharmacology. Recent Results in Cancer Research, vol 74. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-81488-4_35
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DOI: https://doi.org/10.1007/978-3-642-81488-4_35
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