![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 28, Issue 10, 1141-1145, October 2000
Departments of Medical Oncology The clinical pharmacokinetic behavior of paclitaxel (Taxol) is
distinctly nonlinear, with disproportional increases in systemic exposure with an increase in dose. We have recently shown that Cremophor EL, the formulation vehicle used for i.v. administration of
paclitaxel, alters drug distribution as a result of micellar entrapment
of paclitaxel, and we speculated that the free drug fraction (fu) is
dependent on dose and time-varying concentrations of Cremophor EL in
the central plasma compartment. To test this hypothesis, a reproducible
equilibrium dialysis method has been developed for the measurement of
paclitaxel fu in plasma. Equilibrium dialysis was performed at 37°C
in a humidified atmosphere of 5% CO2 using 2.0-ml
polypropylene test tubes. Experiments were carried out with 260-µl
aliquots of plasma containing a tracer amount of
[G-3H]paclitaxel
with high-specific activity against an equal volume of 0.01 M phosphate
buffer (pH 7.4). Drug concentrations were measured by both
reversed-phase HPLC and liquid scintillation counting. Using this
method, fu has been measured in three patients receiving three
consecutive 3-weekly courses of paclitaxel at dose levels of 135, 175, and 225 mg/m2 and found to range between
0.036 and 0.079. The method was also used to define concentration-time
profiles of unbound drug, estimated from the product of the total
plasma concentration and fu.
(E.B., J.V., P.d.B.,
W.J.L., A.S.),
and Nuclear Medicine (M.P., D.B.),
Rotterdam
Cancer Institute
(Daniel den Hoed Kliniek)
and University
Hospital
Rotterdam, The Netherlands
This article has been cited by other articles:
|
|
 |
|
  E. R. Gardner, W. L. Dahut, C. D. Scripture, J. Jones, J. B. Aragon-Ching, N. Desai, M. J. Hawkins, A. Sparreboom, and W. D. Figg Randomized Crossover Pharmacokinetic Study of Solvent-Based Paclitaxel and nab-Paclitaxel Clin. Cancer Res., July 1, 2008; 14(13): 4200 - 4205. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sparreboom, A. C. Wolff, R. H.J. Mathijssen, E. Chatelut, E. K. Rowinsky, J. Verweij, and S. D. Baker Evaluation of Alternate Size Descriptors for Dose Calculation of Anticancer Drugs in the Obese J. Clin. Oncol., October 20, 2007; 25(30): 4707 - 4713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Desai, V. Trieu, Z. Yao, L. Louie, S. Ci, A. Yang, C. Tao, T. De, B. Beals, D. Dykes, et al. Increased Antitumor Activity, Intratumor Paclitaxel Concentrations, and Endothelial Cell Transport of Cremophor-Free, Albumin-Bound Paclitaxel, ABI-007, Compared with Cremophor-Based Paclitaxel Clin. Cancer Res., February 15, 2006; 12(4): 1317 - 1324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Henningsson, S. Marsh, W. J. Loos, M. O. Karlsson, A. Garsa, K. Mross, S. Mielke, L. Vigano, A. Locatelli, J. Verweij, et al. Association of CYP2C8, CYP3A4, CYP3A5, and ABCB1 Polymorphisms with the Pharmacokinetics of Paclitaxel Clin. Cancer Res., November 15, 2005; 11(22): 8097 - 8104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Polee, A. Sparreboom, F. A. L. M. Eskens, R. Hoekstra, J. van de Schaaf, J. Verweij, G. Stoter, and A. van der Gaast A Phase I and Pharmacokinetic Study of Weekly Paclitaxel and Carboplatin in Patients with Metastatic Esophageal Cancer Clin. Cancer Res., March 15, 2004; 10(6): 1928 - 1934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. W. Ng, W. D. Figg, and A. Sparreboom Taxane-Mediated Antiangiogenesis in Vitro: Influence of Formulation Vehicles and Binding Proteins Cancer Res., February 1, 2004; 64(3): 821 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Smorenburg, A. Sparreboom, M. Bontenbal, G. Stoter, K. Nooter, and J. Verweij Randomized Cross-Over Evaluation of Body-Surface Area-Based Dosing Versus Flat-Fixed Dosing of Paclitaxel J. Clin. Oncol., January 15, 2003; 21(2): 197 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sparreboom, A. C. Wolff, J. Verweij, Y. Zabelina, D. M. van Zomeren, G. L. McIntire, C. S. Swindell, R. C. Donehower, and S. D. Baker Disposition of Docosahexaenoic Acid-Paclitaxel, a Novel Taxane, in Blood: In Vitro and Clinical Pharmacokinetic Studies Clin. Cancer Res., January 1, 2003; 9(1): 151 - 159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Gelderblom, J. Verweij, D. M. van Zomeren, D. Buijs, L. Ouwens, K. Nooter, G. Stoter, and A. Sparreboom Influence of Cremophor EL on the Bioavailability of Intraperitoneal Paclitaxel Clin. Cancer Res., April 1, 2002; 8(4): 1237 - 1241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Gelderblom, K. Mross, A. J. ten Tije, D. Behringer, S. Mielke, D. M. van Zomeren, J. Verweij, and A. Sparreboom Comparative Pharmacokinetics of Unbound Paclitaxel During 1- and 3-Hour Infusions J. Clin. Oncol., January 15, 2002; 20(2): 574 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Henningsson, M. O. Karlsson, L. Vigano, L. Gianni, J. Verweij, and A. Sparreboom Mechanism-Based Pharmacokinetic Model for Paclitaxel J. Clin. Oncol., October 15, 2001; 19(20): 4065 - 4073. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
