Preliminary study on carprofen concentration measurements after transcutaneous treatment with Vetdrop® in a microfracture joint defect model in sheep

Abstract

Background: The present preliminary study describes concentration time courses of the NSAID carprofen in the plasma and synovial fluid in a microfrature sheep model after transcutaneous treatments with a novel application device (Vetdrop®). To treat circumscribed inflammatory processes a transcutaneous application device could potentially be beneficial. After transcutaneous application normally lower systemic concentrations are measured which may reduce the incidence of side effects, whereas efficacy is still maintained. In this study carprofen was used based on its capacity to provide analgesia after orthopaedic procedures in sheep and it is considered that it may have a positive influence on the healing of cartilage in low concentrations.

Results: In all transcutaneously treated animals, carprofen plasma concentrations exceeded those of synovial fluid, although plasma levels remained significantly reduced (300-fold) as compared to carprofen administered intravenously. Furthermore, in contrast to the intravenously treated animals, a modest accumulation of carprofen in plasma and synovial fluid was observed in the transcutaneously treated animals over the 6-week treatment period.

Conclusions: The transcutaneously administered carprofen using the Vetdrop® device penetrated the skin and both, plasma- and synovial concentrations could be measured repeatedly over time. This novel device may be considered a valuable transcutaneous drug delivery system.

Figure 1

Treatment procedure. A. The applicator was held in a 90° angle to the application site. B. An area of approximately 10 cm2 was treated. C. Treatment area.

Figure 2

US performance for synovial fluid sample taking. A. Positioning of sheep. B. Setting how synovial fluid was taken. C. Position of the sheep's limb to expose the medial articular pocket.

Figure 3

Carprofen plasma and synovial fluid levels. Overview of the blood plasma (A-C) and synovial fluid (E) carprofen levels of the transcutaneous treated groups 3 & 4 and the blood plasma levels of the intravenous treated group 6 (D).