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The co-solvent Cremophor EL limits absorption of orally administered paclitaxel in cancer patients

The purpose of this study was to investigate the effect of the co-solvents Cremophor EL and polysorbate 80 on the absorption of orally administered paclitaxel. 6 patients received in a randomized setting, one week apart oral paclitaxel 60 mg m(−2) dissolved in polysorbate 80 or Cremophor EL. For 3 p...

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Autores principales: Malingré, M M, Schellens, J H M, Tellingen, O Van, Ouwehand, M, Bardelmeijer, H A, Rosing, H, Koopman, F J, Schot, M E, Huinink, W W Ten Bokkel, Beijnen, J H
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363961/
https://www.ncbi.nlm.nih.gov/pubmed/11720431
http://dx.doi.org/10.1054/bjoc.2001.2118
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author Malingré, M M
Schellens, J H M
Tellingen, O Van
Ouwehand, M
Bardelmeijer, H A
Rosing, H
Koopman, F J
Schot, M E
Huinink, W W Ten Bokkel
Beijnen, J H
author_facet Malingré, M M
Schellens, J H M
Tellingen, O Van
Ouwehand, M
Bardelmeijer, H A
Rosing, H
Koopman, F J
Schot, M E
Huinink, W W Ten Bokkel
Beijnen, J H
author_sort Malingré, M M
collection PubMed
description The purpose of this study was to investigate the effect of the co-solvents Cremophor EL and polysorbate 80 on the absorption of orally administered paclitaxel. 6 patients received in a randomized setting, one week apart oral paclitaxel 60 mg m(−2) dissolved in polysorbate 80 or Cremophor EL. For 3 patients the amount of Cremophor EL was 5 ml m(−2), for the other three 15 ml m(−2). Prior to paclitaxel administration patients received 15 mg kg(−1) oral cyclosporin A to enhance the oral absorption of the drug. Paclitaxel formulated in polysorbate 80 resulted in a significant increase in the maximal concentration (C (max)) and area under the concentration–time curve (AUC) of paclitaxel in comparison with the Cremophor EL formulations (P = 0.046 for both parameters). When formulated in Cremophor EL 15 ml m(−2), paclitaxel C (max) and AUC values were 0.10 ± 0.06 μM and 1.29 ± 0.99 μM h(−1), respectively, whereas these values were 0.31 ± 0.06 μM and 2.61 ± 1.54 μM h(−1), respectively, when formulated in polysorbate 80. Faecal data revealed a decrease in excretion of unchanged paclitaxel for the polysorbate 80 formulation compared to the Cremophor EL formulations. The amount of paclitaxel excreted in faeces was significantly correlated with the amount of Cremophor EL excreted in faeces (P = 0.019). When formulated in Cremophor EL 15 ml m(−2), paclitaxel excretion in faeces was 38.8 ± 13.0% of the administered dose, whereas this value was 18.3 ±15.5% for the polysorbate 80 formulation. The results show that the co-solvent Cremophor EL is an important factor limiting the absorption of orally administered paclitaxel from the intestinal lumen. They highlight the need for designing a better drug formulation in order to increase the usefulness of the oral route of paclitaxel © 2001 Cancer Research Campaign   http://www.bjcancer.com
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spelling pubmed-23639612009-09-10 The co-solvent Cremophor EL limits absorption of orally administered paclitaxel in cancer patients Malingré, M M Schellens, J H M Tellingen, O Van Ouwehand, M Bardelmeijer, H A Rosing, H Koopman, F J Schot, M E Huinink, W W Ten Bokkel Beijnen, J H Br J Cancer Regular Article The purpose of this study was to investigate the effect of the co-solvents Cremophor EL and polysorbate 80 on the absorption of orally administered paclitaxel. 6 patients received in a randomized setting, one week apart oral paclitaxel 60 mg m(−2) dissolved in polysorbate 80 or Cremophor EL. For 3 patients the amount of Cremophor EL was 5 ml m(−2), for the other three 15 ml m(−2). Prior to paclitaxel administration patients received 15 mg kg(−1) oral cyclosporin A to enhance the oral absorption of the drug. Paclitaxel formulated in polysorbate 80 resulted in a significant increase in the maximal concentration (C (max)) and area under the concentration–time curve (AUC) of paclitaxel in comparison with the Cremophor EL formulations (P = 0.046 for both parameters). When formulated in Cremophor EL 15 ml m(−2), paclitaxel C (max) and AUC values were 0.10 ± 0.06 μM and 1.29 ± 0.99 μM h(−1), respectively, whereas these values were 0.31 ± 0.06 μM and 2.61 ± 1.54 μM h(−1), respectively, when formulated in polysorbate 80. Faecal data revealed a decrease in excretion of unchanged paclitaxel for the polysorbate 80 formulation compared to the Cremophor EL formulations. The amount of paclitaxel excreted in faeces was significantly correlated with the amount of Cremophor EL excreted in faeces (P = 0.019). When formulated in Cremophor EL 15 ml m(−2), paclitaxel excretion in faeces was 38.8 ± 13.0% of the administered dose, whereas this value was 18.3 ±15.5% for the polysorbate 80 formulation. The results show that the co-solvent Cremophor EL is an important factor limiting the absorption of orally administered paclitaxel from the intestinal lumen. They highlight the need for designing a better drug formulation in order to increase the usefulness of the oral route of paclitaxel © 2001 Cancer Research Campaign   http://www.bjcancer.com Nature Publishing Group 2001-11 /pmc/articles/PMC2363961/ /pubmed/11720431 http://dx.doi.org/10.1054/bjoc.2001.2118 Text en Copyright © 2001 Cancer Research Campaign https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Regular Article
Malingré, M M
Schellens, J H M
Tellingen, O Van
Ouwehand, M
Bardelmeijer, H A
Rosing, H
Koopman, F J
Schot, M E
Huinink, W W Ten Bokkel
Beijnen, J H
The co-solvent Cremophor EL limits absorption of orally administered paclitaxel in cancer patients
title The co-solvent Cremophor EL limits absorption of orally administered paclitaxel in cancer patients
title_full The co-solvent Cremophor EL limits absorption of orally administered paclitaxel in cancer patients
title_fullStr The co-solvent Cremophor EL limits absorption of orally administered paclitaxel in cancer patients
title_full_unstemmed The co-solvent Cremophor EL limits absorption of orally administered paclitaxel in cancer patients
title_short The co-solvent Cremophor EL limits absorption of orally administered paclitaxel in cancer patients
title_sort co-solvent cremophor el limits absorption of orally administered paclitaxel in cancer patients
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363961/
https://www.ncbi.nlm.nih.gov/pubmed/11720431
http://dx.doi.org/10.1054/bjoc.2001.2118
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