Comparative preclinical and clinical pharmacokinetics of a Cremophor-free, nanoparticle albumin-bound paclitaxel (ABI-007) and paclitaxel formulated in cremophor (Taxol)

Alex Sparreboom*, Charity D. Scripture, Vuong Trieu, Paul J. Williams, Tapas De, Andrew Yang, Bridget Beals, William D. Figg, Michael Hawkins, Neil Desai

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

446 Scopus citations

Abstract

Purpose: To compare the preclinical and clinical pharmacokinetic properties of paclitaxel formulated as a Cremophor-free, albumin-bound nanoparticle (ABI-007) and formulated in Cremophor-ethanol (Taxol). Experimental Design: ABI-007 and Taxol were given i.v. to Harlan Sprague-Dawley male rats to determine pharmacokinetic and drug disposition. Paclitaxel pharmacokinetic properties also were assessed in 27 patients with advanced solid tumors who were randomly assigned to treatment with ABI-007 (260 mg/m2, 30 minutes; n = 14) or Taxol (175 mg/m2, 3 hours; n = 13), with cycles repeated every 3 weeks. Results: The volume of distribution at steady state and clearance for paclitaxel formulated as Cremophor-free nanoparticle ABI-007 were significantly greater than those for paclitaxel formulated with Cremophor (Taxol) in rats. Fecal excretion was the main elimination pathway with both formulations. Consistent with the preclinical data, paclitaxel clearance and volume of distribution were significantly higher for ABI-007 than for Taxol in humans [21.13 versus 14.76 L/h/m2 (P = 0.048) and 663.8 versus 433.4 L/m2 (P = 0.040), respectively]. Conclusions: Paclitaxel formulated as ABI-007 differs from paclitaxel formulated as Taxol, with a higher plasma clearance and a larger volume of distribution. This finding is consistent with the absence of paclitaxel-sequestering Cremophor micelles after administration of ABI-007. This unique property of ABI-007 could be important for its therapeutic effectiveness.

Original languageEnglish
Pages (from-to)4136-4143
Number of pages8
JournalClinical Cancer Research
Volume11
Issue number11
DOIs
StatePublished - 1 Jun 2005
Externally publishedYes

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