Nanoparticle Albumin-bound Paclitaxel: a Novel Cremphor-EL®-free Formulation of Paclitaxel

Thomas E Stinchcombe

Disclosures

Nanomedicine. 2007;2(4):415-423. 

In This Article

Pharmacokinetics

Nonlinear pharmacokinetic behavior is usually caused by the saturation of drug elimination pathways, and higher levels of the drug in the plasma reflect a higher amount of drug in the tissues. The pharmacokinetics of CrEL-paclitaxel in patients has been described as pseudo-nonlinear owing to the influence of CrEL on paclitaxel pharmacokinetics.[13] The entrapment of paclitaxel in plasma by CrEL in plasma, probably by inclusion within micelles, is the cause of the nonlinear pharmacokinetics.[13] The micelles act as the principal carrier of paclitaxel in the systemic circulation.[14] The fraction of paclitaxel in plasma that is available for distribution and elimination (‘free' paclitaxel) is a function of the CrEL level. The total percentage of paclitaxel contained within micelles increases disproportionately with the higher doses of CrEL associated with higher doses of CrEL-paclitaxel.[14] The CrEL levels may vary depending on the infusion time of paclitaxel.[13] Linear plasma pharmacokinetics are observed when paclitaxel is administered in a CrEL-free formulation.[15] The entrapment of paclitaxel within CrEL micelles may diminish clearance and prolong exposure to higher concentrations of paclitaxel, which may contribute to the systemic toxicities of CrEL-paclitaxel treatment.

A clinical trial comparing the pharmacokinetics of nab-paclitaxel (260 mg/m2 over 30 min) and CrEL-paclitaxel (175 mg/m2 over 3 h) was performed in 27 patients.[16] The mean areas under the curve (AUC) for nab- and CrEL-paclitaxel were similar, despite the difference in the dose, and the half-lives of paclitaxel were also similar (21.6 h for nab-paclitaxel vs 20.5 h for CrEL-paclitaxel). The nab-paclitaxel formulation had a significantly higher plasma clearance and volume of distribution than the CrEL-paclitaxel. The pharmacokinetics of nab-paclitaxel are consistent with the absence of paclitaxel-sequestering CrEL micelles.

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