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Co-administration of GF120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients

Oral bioavailability of paclitaxel is very low, which is due to efficient transport of the drug by the intestinal drug efflux pump P-glycoprotein (P-gp). We have recently demonstrated that the oral bioavailability of paclitaxel can be increased at least 7-fold by co-administration of the P-gp blocke...

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Autores principales: Malingré, M M, Beijnen, J H, Rosing, H, Koopman, F J, Jewell, R C, Paul, E M, Huinink, W W Ten Bokkel, Schellens, J H M
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363627/
https://www.ncbi.nlm.nih.gov/pubmed/11139311
http://dx.doi.org/10.1054/bjoc.2000.1543
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author Malingré, M M
Beijnen, J H
Rosing, H
Koopman, F J
Jewell, R C
Paul, E M
Huinink, W W Ten Bokkel
Schellens, J H M
author_facet Malingré, M M
Beijnen, J H
Rosing, H
Koopman, F J
Jewell, R C
Paul, E M
Huinink, W W Ten Bokkel
Schellens, J H M
author_sort Malingré, M M
collection PubMed
description Oral bioavailability of paclitaxel is very low, which is due to efficient transport of the drug by the intestinal drug efflux pump P-glycoprotein (P-gp). We have recently demonstrated that the oral bioavailability of paclitaxel can be increased at least 7-fold by co-administration of the P-gp blocker cyclosporin A (CsA). Now we tested the potent alternative orally applicable non-immunosuppressive P-gp blocker GF120918. Six patients received one course of oral paclitaxel of 120 mg/m(2) in combination with 1000 mg oral GF120918 (GG918, GW0918). Patients received intravenous (i.v.) paclitaxel 175 mg/m(2) as a 3-hour infusion during subsequent courses. The mean area under the plasma concentration–time curve (AUC) of paclitaxel after oral drug administration in combination with GF120918 was 3.27 ± 1.67 μM.h. In our previously performed study of 120 mg/m(2) oral paclitaxel in combination with CsA the mean AUC of paclitaxel was 2.55 ± 2.29 μM.h. After i.v. administration of paclitaxel the mean AUC was 15.92( )± 2.46 μM.h. The oral combination of paclitaxel with GF120918 was well tolerated. The increase in systemic exposure to paclitaxel in combination with GF120918 is of the same magnitude as in combination with CsA. GF120918 is a good and safe alternative for CsA and may enable chronic oral therapy with paclitaxel. © 2001 Cancer Research Campaign http://www.bjcancer.com
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spelling pubmed-23636272009-09-10 Co-administration of GF120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients Malingré, M M Beijnen, J H Rosing, H Koopman, F J Jewell, R C Paul, E M Huinink, W W Ten Bokkel Schellens, J H M Br J Cancer Regular Article Oral bioavailability of paclitaxel is very low, which is due to efficient transport of the drug by the intestinal drug efflux pump P-glycoprotein (P-gp). We have recently demonstrated that the oral bioavailability of paclitaxel can be increased at least 7-fold by co-administration of the P-gp blocker cyclosporin A (CsA). Now we tested the potent alternative orally applicable non-immunosuppressive P-gp blocker GF120918. Six patients received one course of oral paclitaxel of 120 mg/m(2) in combination with 1000 mg oral GF120918 (GG918, GW0918). Patients received intravenous (i.v.) paclitaxel 175 mg/m(2) as a 3-hour infusion during subsequent courses. The mean area under the plasma concentration–time curve (AUC) of paclitaxel after oral drug administration in combination with GF120918 was 3.27 ± 1.67 μM.h. In our previously performed study of 120 mg/m(2) oral paclitaxel in combination with CsA the mean AUC of paclitaxel was 2.55 ± 2.29 μM.h. After i.v. administration of paclitaxel the mean AUC was 15.92( )± 2.46 μM.h. The oral combination of paclitaxel with GF120918 was well tolerated. The increase in systemic exposure to paclitaxel in combination with GF120918 is of the same magnitude as in combination with CsA. GF120918 is a good and safe alternative for CsA and may enable chronic oral therapy with paclitaxel. © 2001 Cancer Research Campaign http://www.bjcancer.com Nature Publishing Group 2001-01 2001-01-01 /pmc/articles/PMC2363627/ /pubmed/11139311 http://dx.doi.org/10.1054/bjoc.2000.1543 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
Beijnen, J H
Rosing, H
Koopman, F J
Jewell, R C
Paul, E M
Huinink, W W Ten Bokkel
Schellens, J H M
Co-administration of GF120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients
title Co-administration of GF120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients
title_full Co-administration of GF120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients
title_fullStr Co-administration of GF120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients
title_full_unstemmed Co-administration of GF120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients
title_short Co-administration of GF120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients
title_sort co-administration of gf120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363627/
https://www.ncbi.nlm.nih.gov/pubmed/11139311
http://dx.doi.org/10.1054/bjoc.2000.1543
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