Comparative Preclinical and Clinical Pharmacokinetics of a Cremophor-Free, Nanoparticle Albumin-Bound Paclitaxel (ABI-007) and Paclitaxel Formulated in Cremophor (Taxol)
Purpose:To compare the preclinical and clinical pharmacokinetic properties of paclitaxel formulated
as a Cremophor-free, albumin-bound nanoparticle (ABI-007) and formulated in Cremophorethanol
Experimental Design: ABI-007 andTaxol were giveni.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
, 3 0 minutes; n = 14) or Taxol (175 mg/m2
, 3hours; n = 13 ), with
cycles repeated every 3weeks.
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 forTaxol in humans [21.13versus 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 asTaxol, 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.