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Chemical Compound Review

Avlinox     2-hydroxyethyl (Z,12R)-12-hydroxyoctadec-9...

Synonyms: Cremophor-El, Cremophor-E1, Prodhyphore A, Prodhyphore E, Prodhyphore O, ...
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Disease relevance of Avlinox


High impact information on Avlinox

  • Experiments with one or more individual sera indicated the above effect was due to Cremophor EL plus ethanol, that increased formation of Bb also occurred, that the drug-induced rise in SC5b-9 was inhibited by sCR1, and that EGTA/Mg2+ partially inhibited SC5b-9 formation and stimulated Bb formation [1].
  • The clinical formulation of paclitaxel contains 50% Cremophor EL, a polyethoxylated castor oil vehicle (carrier) that can reverse multidrug resistance (MDR) mediated by P-glycoprotein [6].
  • Measurement of cremophor EL following taxol: plasma levels sufficient to reverse drug exclusion mediated by the multidrug-resistant phenotype [7].
  • We hypothesize that this is caused by the association of paclitaxel in the circulation with Cremophor EL, the distribution of which is linked to total blood volume, and thus to BSA [8].
  • These data demonstrate that Cremophor EL has a profound effect on the pharmacokinetics of paclitaxel im mice [9].

Chemical compound and disease context of Avlinox


Biological context of Avlinox

  • The purpose of the present study was to characterize the distribution and elimination kinetics of the paclitaxel vehicle Cremophor EL (CrEL), a polyoxyethylated castor oil that can modulate P-glycoprotein-mediated multidrug resistance in vitro [13].
  • Influence of Cremophor El on the bioavailability of intraperitoneal paclitaxel [14].
  • PURPOSE: The shortening of infusion time from 3 to 1 hour decreases the systemic exposure (area under the curve, AUC) of total and unbound paclitaxel but increases the AUC of its vehicle Cremophor EL, whereas the time above total paclitaxel concentrations of 0.05 micromol/L (T >0.05) remains almost constant [4].
  • We mixed PCT with either a biodegradable polymeric solubilizer, HySolv, or Cremophor EL for bimonthly systemic treatments and injected water-soluble lipopolymer (WSLP)/p2CMVmIL-12 (plasmid encoding IL12 gene) complexes locally every week [15].
  • We investigated the effects of Cremophor-EL on the cardiac output (CO); mean arterial pressure (MAP); and hepatic, renal and pancreatic blood flow in the anesthesized canine model [16].

Anatomical context of Avlinox


Associations of Avlinox with other chemical compounds


Gene context of Avlinox


Analytical, diagnostic and therapeutic context of Avlinox

  • Cremophor EL levels were determined by a novel high-performance liquid chromatography procedure [9].
  • PATIENTS AND METHODS: Paclitaxel and Cremophor EL (CrEL) concentrations were obtained from 23 female and three male patients (50 courses in total) with different cancer types that received paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) (135 to 225 mg/m(2)) as 3- or 24-hour intravenous infusions [29].
  • Cremophor EL may prove to be a relatively pharmacologically inactive addition to chemotherapeutic protocols which may be able to reverse the MDR phenotype in tumors and also help to prevent the selection of MDR cell variants from within a tumor cell population during chemotherapy [17].
  • Undetectable Cremophor EL levels after oral administration may have a very beneficial influence on the safety of the treatment with oral paclitaxel [30].
  • The absence of Cremophor EL may permit ABI-007 to be administered without the premedications used routinely for the prevention of hypersensitivity reactions [31].


  1. Complement activation by Cremophor EL as a possible contributor to hypersensitivity to paclitaxel: an in vitro study. Szebeni, J., Muggia, F.M., Alving, C.R. J. Natl. Cancer Inst. (1998) [Pubmed]
  2. Cremophor EL, solvent for paclitaxel, and toxicity. Liebmann, J., Cook, J.A., Mitchell, J.B. Lancet (1993) [Pubmed]
  3. Human pharmacokinetic characterization and in vitro study of the interaction between doxorubicin and paclitaxel in patients with breast cancer. Gianni, L., Viganò, L., Locatelli, A., Capri, G., Giani, A., Tarenzi, E., Bonadonna, G. J. Clin. Oncol. (1997) [Pubmed]
  4. Association of Paclitaxel pharmacokinetics with the development of peripheral neuropathy in patients with advanced cancer. Mielke, S., Sparreboom, A., Steinberg, S.M., Gelderblom, H., Unger, C., Behringer, D., Mross, K. Clin. Cancer Res. (2005) [Pubmed]
  5. Cholestasis in the rat by means of intravenous administration of cyclosporine vehicle, Cremophor EL. Roman, I.D., Monte, M.J., Esteller, A., Jimenez, R. Transplantation (1989) [Pubmed]
  6. Cremophor pharmacokinetics in patients receiving 3-, 6-, and 24-hour infusions of paclitaxel. Rischin, D., Webster, L.K., Millward, M.J., Linahan, B.M., Toner, G.C., Woollett, A.M., Morton, C.G., Bishop, J.F. J. Natl. Cancer Inst. (1996) [Pubmed]
  7. Measurement of cremophor EL following taxol: plasma levels sufficient to reverse drug exclusion mediated by the multidrug-resistant phenotype. Webster, L., Linsenmeyer, M., Millward, M., Morton, C., Bishop, J., Woodcock, D. J. Natl. Cancer Inst. (1993) [Pubmed]
  8. Randomized cross-over evaluation of body-surface area-based dosing versus flat-fixed dosing of paclitaxel. Smorenburg, C.H., Sparreboom, A., Bontenbal, M., Stoter, G., Nooter, K., Verweij, J. J. Clin. Oncol. (2003) [Pubmed]
  9. Nonlinear pharmacokinetics of paclitaxel in mice results from the pharmaceutical vehicle Cremophor EL. Sparreboom, A., van Tellingen, O., Nooijen, W.J., Beijnen, J.H. Cancer Res. (1996) [Pubmed]
  10. Phase I clinical trial of BMS-247550, a derivative of epothilone B, using accelerated titration 2B design. Gadgeel, S.M., Wozniak, A., Boinpally, R.R., Wiegand, R., Heilbrun, L.K., Jain, V., Parchment, R., Colevas, D., Cohen, M.B., LoRusso, P.M. Clin. Cancer Res. (2005) [Pubmed]
  11. Effect of combination of suboptimal concentrations of P-glycoprotein blockers on the proliferation of MDR1 gene expressing cells. Hwang, M., Ahn, C.H., Pine, P.S., Yin, J.J., Hrycyna, C.A., Licht, T., Aszalos, A. Int. J. Cancer (1996) [Pubmed]
  12. Biodistribution of O6-benzylguanine and its effectiveness against human brain tumor xenografts when given in polyethylene glycol or cremophor-EL. Dolan, M.E., Pegg, A.E., Moschel, R.C., Vishnuvajjala, B.R., Flora, K.P., Grever, M.R., Friedman, H.S. Cancer Chemother. Pharmacol. (1994) [Pubmed]
  13. Disposition of Cremophor EL in humans limits the potential for modulation of the multidrug resistance phenotype in vivo. Sparreboom, A., Verweij, J., van der Burg, M.E., Loos, W.J., Brouwer, E., Viganò, L., Locatelli, A., de Vos, A.I., Nooter, K., Stoter, G., Gianni, L. Clin. Cancer Res. (1998) [Pubmed]
  14. Influence of Cremophor El on the bioavailability of intraperitoneal paclitaxel. Gelderblom, H., Verweij, J., van Zomeren, D.M., Buijs, D., Ouwens, L., Nooter, K., Stoter, G., Sparreboom, A. Clin. Cancer Res. (2002) [Pubmed]
  15. Combination of local, nonviral IL12 gene therapy and systemic paclitaxel treatment in a metastatic breast cancer model. Janát-Amsbury, M.M., Yockman, J.W., Lee, M., Kern, S., Furgeson, D.Y., Bikram, M., Kim, S.W. Mol. Ther. (2004) [Pubmed]
  16. The hemodynamic effects of Cremophor-EL. Bowers, V.D., Locker, S., Ames, S., Jennings, W., Corry, R.J. Transplantation (1991) [Pubmed]
  17. Reversal of the multidrug resistance phenotype with cremophor EL, a common vehicle for water-insoluble vitamins and drugs. Woodcock, D.M., Jefferson, S., Linsenmeyer, M.E., Crowther, P.J., Chojnowski, G.M., Williams, B., Bertoncello, I. Cancer Res. (1990) [Pubmed]
  18. Vascular effects of cyclosporine A in vivo and in vitro. Ferns, G., Reidy, M., Ross, R. Am. J. Pathol. (1990) [Pubmed]
  19. Cyclosporine and cremaphor modulate von Willebrand factor release from cultured human endothelial cells. Collins, P., Wilkie, M., Razak, K., Abbot, S., Harley, S., Bax, C., Zaidi, M., Blake, D., Cunningham, J., Newland, A. Transplantation (1993) [Pubmed]
  20. Emulsifier for intravenous cyclosporin inhibits neurite outgrowth, causes deficits in rapid axonal transport and leads to structural abnormalities in differentiating N1E.115 neuroblastoma. Brat, D.J., Windebank, A.J., Brimijoin, S. J. Pharmacol. Exp. Ther. (1992) [Pubmed]
  21. Decreased DNA topoisomerase II in daunorubicin-resistant Ehrlich ascites tumor cells. Friche, E., Danks, M.K., Schmidt, C.A., Beck, W.T. Cancer Res. (1991) [Pubmed]
  22. Hypersensitivity reactions from taxol. Weiss, R.B., Donehower, R.C., Wiernik, P.H., Ohnuma, T., Gralla, R.J., Trump, D.L., Baker, J.R., Van Echo, D.A., Von Hoff, D.D., Leyland-Jones, B. J. Clin. Oncol. (1990) [Pubmed]
  23. Paclitaxel cytotoxicity against human lung cancer cell lines increases with prolonged exposure durations. Georgiadis, M.S., Russell, E.K., Gazdar, A.F., Johnson, B.E. Clin. Cancer Res. (1997) [Pubmed]
  24. Development and validation of a liquid chromatography-tandem mass spectrometry assay for the quantification of docetaxel and paclitaxel in human plasma and oral fluid. Mortier, K.A., Renard, V., Verstraete, A.G., Van Gussem, A., Van Belle, S., Lambert, W.E. Anal. Chem. (2005) [Pubmed]
  25. P450 induction alters paclitaxel pharmacokinetics and tissue distribution with multiple dosing. Gustafson, D.L., Long, M.E., Bradshaw, E.L., Merz, A.L., Kerzic, P.J. Cancer Chemother. Pharmacol. (2005) [Pubmed]
  26. Multidrug resistance phenotype and paclitaxel (Taxol) sensitivity in human renal carcinoma cell lines of different histologic types. Reinecke, P., Schmitz, M., Schneider, E.M., Gabbert, H.E., Gerharz, C.D. Cancer Invest. (2000) [Pubmed]
  27. Induction of apoptosis in MDR1 expressing cells by daunorubicin with combinations of suboptimal concentrations of P-glycoprotein modulators. Aszalos, A., Ladányi, A., Bocsi, J., Szende, B. Cancer Lett. (2001) [Pubmed]
  28. Cremophor EL reversed multidrug resistance in vitro but not in tumor-bearing mouse models. Watanabe, T., Nakayama, Y., Naito, M., Oh-hara, T., Itoh, Y., Tsuruo, T. Anticancer Drugs (1996) [Pubmed]
  29. Mechanism-based pharmacokinetic model for paclitaxel. Henningsson, A., Karlsson, M.O., Viganò, L., Gianni, L., Verweij, J., Sparreboom, A. J. Clin. Oncol. (2001) [Pubmed]
  30. Coadministration of oral cyclosporin A enables oral therapy with paclitaxel. Meerum Terwogt, J.M., Malingré, M.M., Beijnen, J.H., ten Bokkel Huinink, W.W., Rosing, H., Koopman, F.J., van Tellingen, O., Swart, M., Schellens, J.H. Clin. Cancer Res. (1999) [Pubmed]
  31. Phase I and pharmacokinetic study of ABI-007, a Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel. Ibrahim, N.K., Desai, N., Legha, S., Soon-Shiong, P., Theriault, R.L., Rivera, E., Esmaeli, B., Ring, S.E., Bedikian, A., Hortobagyi, G.N., Ellerhorst, J.A. Clin. Cancer Res. (2002) [Pubmed]
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