CMS in 15 µl glass capillaries allows collection and handling of small and exact volumes of blood. Although CMS can also be applied for plasma collection, the full benefit is only achieved with blood collection and analysis.

It has been suggested that oral absorption of low-permeable P-glycoprotein (P-gp) substrates can be increased through saturation of P-gp. For BCS class IV drug substances, saturating P-gp is challenging due to low aqueous solubility. The present study investigated if the BCS IV drug substance etoposide could be solubilized to a concentration saturating P-gp after oral administration.A formulation consisting of 10% (w/v) of pluronic ® F-127 and polyvinylpyrrolidone/vinyl acetate (PVP/VA), and 57% (v/v) ethanol enhanced etoposide's solubility approximately 100 times (16 mg mL -1 ) compared to its aqueous solubility. In vitro, this formulation was stable upon dilution in simulated intestinal fluid. In male Sprague-Dawley rats, oral administration of increasing solubilized etoposide doses using the formulation matrix increased the AUC0-∞ of etoposide dose-proportionally but resulted in a lower absolute oral bioavailability (F) and rate of absorption as compared to control.At the highest investigated dose (100 mg kg -1 ), AUC0-∞ and Cmax were significantly increased by 2.9and 1.4-fold, respectively, compared to control dosed at 20 mg kg -1 . A single oral dose of 20 mg kg -1 zosuquidar followed by 20 mg kg -1 oral etoposide increased F 8.6-fold. In conclusion, a stable formulation with improved etoposide solubility was developed, yet the formulation did not result in increased oral bioavailability of etoposide.