Abstract
We have studied the cytotoxicity of bleomycin (4--10 u/kg/day for 6 days) given by continuous i.p. infusion (using an osmotic minipump) compared to daily i.p. bolus administration, against P388 leukaemic spleen colony-forming-units(LCFU-S). Continuous i.p. bleomycin at 8 u/kg/day caused a 0.5 log greater reduction of LCFU-S than did an identical dose given by intermittent bolus administration. The infusion minipump provided constant bleomycin plasma levels of 0.62 +/- 0.03 mu/ml and a total plasma AUC (area under the plasma decay curve) of 89.0 mu.h/ml for 6 days at 8 u/kg/day. Intermittent bolus bleomycin at 8 u.kg/day had a terminal-phase plasma t1/2 of 15 min and a total 6-day plasma AUC of 90.8mu.h/ml. These pharmacokinetic data validate the osmotic minipump as a constant drug-delivery system, and suggest that the two administration schedules resulted in equal total bleomycin dosages. Although high peak bleomycin plasma levels (i.e. 32 mu/ml) were achieved with the intermittent bolus administration, continuous-infusion bleomycin's greater inhibition of LCFU-S was probably related to the drug's schedule-dependent cell-killing characteristics. The results of this study provide further rationale for the continuing use of infusion bleomycin schedules in cancer patients.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alberts D. S., Chen H. S., Liu R., Himmelstein K. J., Mayersohn M., Perrier D., Gross J., Moon T., Broughton A., Salmon S. E. Bleomycin pharmacokinetics in man. I. Intravenous administration. Cancer Chemother Pharmacol. 1978;1(3):177–181. doi: 10.1007/BF00253118. [DOI] [PubMed] [Google Scholar]
- Alberts D. S., Chen H. S., Mayersohn M., Perrier D., Moon T. E., Gross J. F. Bleomycin pharmacokinetics in man. II. Intracavitary administration. Cancer Chemother Pharmacol. 1979;2(2):127–132. doi: 10.1007/BF00254085. [DOI] [PubMed] [Google Scholar]
- Alberts D. S., van Daalen Wetters T. The effect of phenobarbital on cyclophosphamide antitumor activity. Cancer Res. 1976 Aug;36(8):2785–2789. [PubMed] [Google Scholar]
- Baker L. H., Opipari M. I., Wilson H., Bottomley R., Coltman C. A., Jr Mitomycin C, vincristine, and bleomycin therapy for advanced cervical cancer. Obstet Gynecol. 1978 Aug;52(2):146–150. [PubMed] [Google Scholar]
- Broughton A., Strong J. E. Radioimmunoassay of bleomycin. Cancer Res. 1976 Apr;36(4):1418–1421. [PubMed] [Google Scholar]
- Sikic B. I., Collins J. M., Mimnaugh E. G., Gram T. E. Improved therapeutic index of bleomycin when administered by continuous infusion in mice. Cancer Treat Rep. 1978 Dec;62(12):2011–2017. [PubMed] [Google Scholar]
- Skipper H. E., Schabel F. M., Jr, Wilcox W. S. Experimental evaluation of potential anticancer agents. XXI. Scheduling of arabinosylcytosine to take advantage of its S-phase specificity against leukemia cells. Cancer Chemother Rep. 1967 Jun;51(3):125–165. [PubMed] [Google Scholar]