Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1997;76(9):1181–1183. doi: 10.1038/bjc.1997.530

Enhanced oral bioavailability of paclitaxel in mice treated with the P-glycoprotein blocker SDZ PSC 833.

J van Asperen 1, O van Tellingen 1, A Sparreboom 1, A H Schinkel 1, P Borst 1, W J Nooijen 1, J H Beijnen 1
PMCID: PMC2228133  PMID: 9365166

Abstract

Inhibition of intestinal P-glycoprotein might enhance the absorption of orally administered P-glycoprotein substrate drugs. We show here a 10-fold increased oral bioavailability of paclitaxel in mice treated with the P-glycoprotein blocker SDZ PSC 833. These results encourage further research on the development of a clinically useful oral formulation of paclitaxel.

Full text

PDF
1181

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Boesch D., Gavériaux C., Jachez B., Pourtier-Manzanedo A., Bollinger P., Loor F. In vivo circumvention of P-glycoprotein-mediated multidrug resistance of tumor cells with SDZ PSC 833. Cancer Res. 1991 Aug 15;51(16):4226–4233. [PubMed] [Google Scholar]
  2. Croop J. M., Raymond M., Haber D., Devault A., Arceci R. J., Gros P., Housman D. E. The three mouse multidrug resistance (mdr) genes are expressed in a tissue-specific manner in normal mouse tissues. Mol Cell Biol. 1989 Mar;9(3):1346–1350. doi: 10.1128/mcb.9.3.1346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Eiseman J. L., Eddington N. D., Leslie J., MacAuley C., Sentz D. L., Zuhowski M., Kujawa J. M., Young D., Egorin M. J. Plasma pharmacokinetics and tissue distribution of paclitaxel in CD2F1 mice. Cancer Chemother Pharmacol. 1994;34(6):465–471. doi: 10.1007/BF00685656. [DOI] [PubMed] [Google Scholar]
  4. Fisher G. A., Lum B. L., Hausdorff J., Sikic B. I. Pharmacological considerations in the modulation of multidrug resistance. Eur J Cancer. 1996 Jun;32A(6):1082–1088. doi: 10.1016/0959-8049(96)00111-6. [DOI] [PubMed] [Google Scholar]
  5. Fujita H., Okamoto M., Takao A., Mase H., Kojima H. [Pharmacokinetics of paclitaxel in experimental animals. Part 1. Blood level]. Gan To Kagaku Ryoho. 1994 Apr;21(5):653–658. [PubMed] [Google Scholar]
  6. Harris J. W., Rahman A., Kim B. R., Guengerich F. P., Collins J. M. Metabolism of taxol by human hepatic microsomes and liver slices: participation of cytochrome P450 3A4 and an unknown P450 enzyme. Cancer Res. 1994 Aug 1;54(15):4026–4035. [PubMed] [Google Scholar]
  7. Huizing M. T., Misser V. H., Pieters R. C., ten Bokkel Huinink W. W., Veenhof C. H., Vermorken J. B., Pinedo H. M., Beijnen J. H. Taxanes: a new class of antitumor agents. Cancer Invest. 1995;13(4):381–404. doi: 10.3109/07357909509031919. [DOI] [PubMed] [Google Scholar]
  8. Keller R. P., Altermatt H. J., Nooter K., Poschmann G., Laissue J. A., Bollinger P., Hiestand P. C. SDZ PSC 833, a non-immunosuppressive cyclosporine: its potency in overcoming P-glycoprotein-mediated multidrug resistance of murine leukemia. Int J Cancer. 1992 Feb 20;50(4):593–597. doi: 10.1002/ijc.2910500418. [DOI] [PubMed] [Google Scholar]
  9. McGuire W. P., Hoskins W. J., Brady M. F., Kucera P. R., Partridge E. E., Look K. Y., Clarke-Pearson D. L., Davidson M. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 1996 Jan 4;334(1):1–6. doi: 10.1056/NEJM199601043340101. [DOI] [PubMed] [Google Scholar]
  10. Rowinsky E. K., Donehower R. C. Paclitaxel (taxol) N Engl J Med. 1995 Apr 13;332(15):1004–1014. doi: 10.1056/NEJM199504133321507. [DOI] [PubMed] [Google Scholar]
  11. Schinkel A. H., Smit J. J., van Tellingen O., Beijnen J. H., Wagenaar E., van Deemter L., Mol C. A., van der Valk M. A., Robanus-Maandag E. C., te Riele H. P. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell. 1994 May 20;77(4):491–502. doi: 10.1016/0092-8674(94)90212-7. [DOI] [PubMed] [Google Scholar]
  12. Shet M. S., Fisher C. W., Holmans P. L., Estabrook R. W. Human cytochrome P450 3A4: enzymatic properties of a purified recombinant fusion protein containing NADPH-P450 reductase. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11748–11752. doi: 10.1073/pnas.90.24.11748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sparreboom A., van Asperen J., Mayer U., Schinkel A. H., Smit J. W., Meijer D. K., Borst P., Nooijen W. J., Beijnen J. H., van Tellingen O. Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):2031–2035. doi: 10.1073/pnas.94.5.2031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sparreboom A., van Tellingen O., Nooijen W. J., Beijnen J. H. Determination of paclitaxel and metabolites in mouse plasma, tissues, urine and faeces by semi-automated reversed-phase high-performance liquid chromatography. J Chromatogr B Biomed Appl. 1995 Feb 17;664(2):383–391. doi: 10.1016/0378-4347(94)00495-q. [DOI] [PubMed] [Google Scholar]
  15. Sparreboom A., van Tellingen O., Nooijen W. J., Beijnen J. H. Nonlinear pharmacokinetics of paclitaxel in mice results from the pharmaceutical vehicle Cremophor EL. Cancer Res. 1996 May 1;56(9):2112–2115. [PubMed] [Google Scholar]
  16. Teeter L. D., Becker F. F., Chisari F. V., Li D. J., Kuo M. T. Overexpression of the multidrug resistance gene mdr3 in spontaneous and chemically induced mouse hepatocellular carcinomas. Mol Cell Biol. 1990 Nov;10(11):5728–5735. doi: 10.1128/mcb.10.11.5728. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES