Comparative preclinical and clinical pharmacokinetics of a cremophor-free, nanoparticle albumin-bound paclitaxel (ABI-007) and paclitaxel formulated in Cremophor (Taxol)
| Autor: | Charity D. Scripture, Andrew Yang, Bridget Beals, Paul J. Williams, Alex Sparreboom, Tapas De, Michael J. Hawkins, William D. Figg, Neil Desai, Vuong Trieu |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Cancer Research Paclitaxel Metabolic Clearance Rate Pharmacology Rats Sprague-Dawley chemistry.chemical_compound Albumin bound paclitaxel Pharmacokinetics Albumins Neoplasms Male rats Animals Humans Tissue Distribution Aged Volume of distribution Drug disposition Albumin Middle Aged Preclinical data Antineoplastic Agents Phytogenic Rats body regions Oncology chemistry Area Under Curve Injections Intravenous Female Albumin-Bound Paclitaxel |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 11(11) |
| ISSN: | 1078-0432 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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