Absorption and distribution of etoricoxib in plasma, CSF, and wound tissue in patients following hip surgery—a pilot study

The perioperative administration of selective cyclooxygenase-2 (COX-2)-inhibitors to avoid postoperative pain is an attractive option: they show favorable gastro-intestinal tolerability, lack inhibition of blood coagulation, and carry a low risk of asthmatic attacks. The purpose of this study was to determine the cerebrospinal fluid (CSF), plasma, and tissue pharmacokinetics of orally administered etoricoxib and to compare it with effect data, i.e., COX-2-inhibition in patients after hip surgery. The study was performed in a blinded, randomized, parallel group design. A total of 12 adult patients were included who received 120 mg etoricoxib (n = 8) or placebo (n = 4) on day 1 post-surgery. Samples from plasma, CSF, and tissue exudates were collected over a period of 24 h post-dosing and analyzed for etoricoxib and prostaglandin E2 (PGE2) using liquid chromatography-tandem mass spectrometry and immuno-assay techniques. CSF area under the curve (AUC) [AUCs(O–24h)] for etoricoxib amounted to about 5% of the total AUC in plasma (range: 2–7%). Individual CSF lag times with respect to (50%) peak plasma concentration were ≤2 h in all but one case (median: 1 h). PGE2 production in tissue was significantly blocked by the COX-2 inhibitor starting with the appearance of etoricoxib in tissue and lasting for the whole observation period of 24 h (P < 0.01). In conclusion, etoricoxib reaches the CSF and site of surgery at effective concentrations and reduces PGE2 production at the presumed site of action

Alkyl Polyglucoside-based delivery systems: In vitro/in vivo skin absorption assessment

Skin permeation and penetration assessment is important not only for determining efficacy of a topical product, but also when comparing different formulations during development. This chapter reviews methods for dermal availability assessment of delivery systems, with their advantages and shortcomings, and examples of their practical application with Alkyl Polyglucoside-based preparations. Alkyl Polyglucosides are used in many different delivery systems with various model actives. Systems stabilized with Alkyl Polyglucoside surfactants provide highly satisfactory cutaneous delivery compared with reference samples. This is mainly attributed to the characteristic APG-based colloidal structure and its ability to provide a combined enhancing effect with co-solvents. Microemulsions for dermal/transdermal delivery are also becoming popular due to their high solubilization potential. Alkyl Polyglucoside surfactants are also being considered for development of nanosystems