Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Feb 2002
Entrapment by Cremophor EL decreases the absorption of paclitaxel from the gut.
Recent studies in mice and patients have shown that the low oral bioavailability of paclitaxel can be increased by coadministration of P-glycoprotein blockers. However, in patients an increase in the oral paclitaxel dose from 60 to 300 mg/m(2) does not result in proportionally higher plasma levels. We hypothesized that the surfactant Cremophor EL, present in the formulation of paclitaxel, may be responsible for this nonlinear absorption by entrapping paclitaxel within the intestinal lumen, probably by inclusion in micelles. ⋯ These results show that Cremophor EL prevents efficient uptake of paclitaxel from the gut, probably by entrapment within micelles. Other formulations should be developed for oral therapy with paclitaxel.