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

Abstract

BackgroundThe 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.ResultsIn 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.ConclusionsThe 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.

Pharmacokinetic Appraisal of Carprofen Delivery from Intra-Articular Nanoparticles: A Population Modeling Approach in Rabbits

“…In any case, CP plasma levels resulted to be higher than IC50 for Cox2 [32] both after IV and IA administrations. The lower albumin concentrations in synovial fluid (60%) in rabbits compared to plasma resulted in higher total plasma CP concentrations than in synovial cavity once the distribution equilibrium reached, as also reported in sheep [25] and in horse [2].…”

“…Anatomical similarities of rabbits with other species (dog, cat), suggests the extrapolation of in vivo CP release/absorption to these species. As previously reported [12,24,25], CP disposition was best described by a two-compartment model. The steady-state distribution volume (Vss = 0.1126 L/kg mean live bodyweight) was in line with other results in rabbits [26], dogs 0.1192 L/kg [24] or cats (0.1506 L/kg) [27].…”

Exploratory Assessment of Oxygen Flow–Assisted Cutaneous Administration of Methotrexate for Superficial Basal Cell Carcinoma, Mycosis Fungoides, and Extramammary Paget Disease

“…OFA-LP3 significantly increased the epidermal permeation compared with LP3 alone, as demonstrated by ultrasound cross-sections and tape stripping (Sidler et al, 2014(Sidler et al, , 2013.…”

Analgesia for Sheep in Commercial Production: Where to Next?

“…Carprofen and ketoprofen exist as registered products for cattle in Australia, and as such have received some research interest. Carprofen, in particular is reported to remain at high levels in plasma for a prolonged period [ 356 ], although pharmacokinetic data for carprofen in sheep were not found in the published literature between 2000 and 2019. In sheep, carprofen at 4 mg/kg given either subcutaneously or intramuscularly 90 min prior to the procedure reduced the cortisol and behavioural response to surgical mulesing [ 138 , 139 ], but provided only modest analgesia to lambs undergoing surgical castration and hot knife tail docking [ 256 ].…”