Although EC increased with running speed, OC was insensitive to changes in running speed and, therefore, does not appear to provide a valid index of the underlying EC of running, likely due to the inability of OC to account for variations in substrate use. Therefore, EC should be used as the primary measure of running economy, and for runners, an appropriate scaling with body mass is recommended.

The effects of the non-ionic surfactants polysorbate 20, polysorbate 60, polysorbate 85, cholesteryl poly (24) oxyethylene ether (Solulan C24) and the lanolin-based poly (16) oxyethylene ether (Solulan 16) on the epithelial integrity of monolayers of human intestinal epithelial (Caco-2) cells has been studied using metformin as a model drug. The aim was to identify the surfactants and their optimal concentrations capable of enhancing drug transport while causing no, or only minor, cellular damage. Effects on cell permeability were assessed by measurements of the transport of metformin, a hydrophilic drug, by monitoring transepithelial electrical resistance. Cell viability was determined by the diphenyltetrazolium bromide test (the MTT test). All the surfactants studied demonstrated concentration-dependent effects on cell permeability and cell viability. The effects on transepithelial electrical resistance correlated with cell viability, i.e. increased transepithelial electrical resistance and increased cell-monolayer permeability for metformin corresponded to decreased cell viability. The results indicate that the Solulan and polysorbate surfactants were active as absorption enhancers, Solulan C24 and 16 being more effective than polysorbates 20, 60 or 85, causing an increase in metformin transport at lower concentrations than the polysorbates. Polysorbate 20 exerted its greatest effect at a concentration of 5%-increasing the flux of metformin after 3 h by a factor of around 20 over the control. Large increases in the transport of metformin, especially at surfactant levels of 0.05%, 0.1% and 0.5%, were related to the effect of Solulan C24 and Solulan 16 on the cell permeability. The Caco-2 cell monolayer experiments confirmed the ability, especially of polysorbate 20, Solulan C24 and Solulan 16, to increase the absorption of metformin. The polysorbates increased permeability as a result of solubilisation of membrane components, while Solulans did so by penetrating and solubilising the membrane. Correlation between increase in membrane permeability and the toxicity of the surfactants towards the cell membrane has been established.

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