Entrapment by Cremophor EL decreases the absorption of paclitaxel from the gut

Abstract

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.

Oxidative stress induced by Cremophor EL is not accompanied by changes in NF-κB activation or iNOS expression

“…Adverse effects on hepatobiliary physiology in the rat have also been reported (Román et al, 1989). Moreover, CrEL prevents efficient uptake of paclitaxel from the gut, probably by entrapment within micelles (Bardelmeijer et al, 2002), which may help to explain non-linear absorption of orally administered paclitaxel (Malingré et al, 2000).…”

Effects of Cremophor EL on the absorption of orally administered saquinavir and fexofenadine in healthy subjects

“…In their study, paclitaxel was administered to the Mdr1a/1b knockout mice with either the conventional amount of Cremophor EL (controls) or sevenfold greater amount (test group). As a result, the AUC for paclitaxel was reduced in the test group, and this result suggested that Cremophor EL entrapped paclitaxel in the gastrointestinal lumen by incorporating it into micelles, thus reducing the absorption of the drug [20]. Furthermore, Zastre et al compared the micelle association and Caco-2 cellular accumulation of two structurally homologous P-gp substrates using diblock copolymers, the relatively hydrophobic rhodamine-6 glucronide and the hydrophilic rhodamine 123, at excipient concentrations above and below the cmc [21].…”

Oral bioavailability of a novel paclitaxel formulation (Genetaxyl) administered with cyclosporin A in cancer patients

“…A prior study showed that a large fraction of both paclitaxel and CrEL was recovered unchanged in fecal samples after oral administration of Taxol [21], suggesting that the co-solvent CrEL could limit absorption of orally administrated paclitaxel by forming micelles entrapping the drug, without being itself absorbed [28]. Based on this finding, it was expected that the systemic exposure to paclitaxel after oral administration of Genetaxyl, containing 60% less CrEL as compared with Taxol, would be higher than those after administration of Taxol.…”