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Updated: Aug 6, 2026

Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice
Published on: October 27, 2014
The influence of P-glycoprotein on morphine transport in Caco-2 cells. Comparison with paclitaxel
1School of Pharmacy, Curtin University of Technology, GPO Box U1987, 6845, Perth, Australia. A.P.Crowe@curtin.edu.au
Abstract:
In vitro monolayer studies using Caco-2 cells were employed here to explore P-glycoprotein mediated transport of morphine. Bi-directional transport studies of 10-75 microM morphine showed efflux to be twofold higher than influx (4 x 10(-6) compared to 2 x 10(-6) cm/s) and cellular accumulation in the efflux direction was eightfold higher. The cyclosporin analogue (PSC-833) equilibrated morphine transport in both directions. Depletion of intracellular glutathione had a greater effect on increasing cellular morphine accumulation than P-glycoprotein inhibitors, suggesting a role for glutathione in morphine transport. P-glycoprotein had a substantially greater effect on paclitaxel accumulation, efflux and bi-directional transport than for morphine. Paclitaxel transport was below detection (<0.1 x 10(-6) cm/s) in the influx direction, yet efflux was very high (18.4 x 10(-6) cm/s) and P-glycoprotein inhibition increased accumulation >100-fold. These results reinforce the substantial role P-glycoprotein has in paclitaxel transport. Conversely, P-glycoprotein regulated morphine transport is weak. Nevertheless, morphine transport rates could be doubled when administered with P-glycoprotein substrates. Therefore, increased analgesia through P-glycoprotein inhibition should be possible.
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