Lidocaine is increasingly used in transdermal drug delivery systems for different pain conditions in human medicine whereby several pharmacokinetic studies have demonstrated minimal systemic absorption in men. In the present study, the pharmacokinetics of a lidocaine patch 5% was studied in six dogs. In the first experiment, one single lidocaine patch was applied for 12 h to the lateral side of the thorax after removing the hair either by clipping or by the application of a depilatory agent, according to a two-way crossover design. No potential adverse effects induced by the patches were observed in either group. In dogs with clipped hair, a mean peak plasma lidocaine concentration of 62.94 ng/ml was obtained after 10.67 h. In the depilatory group, a mean peak plasma concentration of 103.55 ng/ml was reached after 9.27 h. Significant differences in the AUC(0 --> infinity), C(max), k(a) and T(1/2a) were noticed between the two groups. No significant differences were found for the elimination parameters and for T(max). In the second experiment, the patches were applied for 60 h to the clipped skin in order to study the absorption kinetics after a prolonged application period. There, the mean peak lidocaine plasma concentration was 45.18 ng/ml achieved after 24 h and a final concentration of 29.37 ng/ml was obtained at 60 h. In conclusion, all dogs tolerated the transdermal lidocaine patch well. The results of this study suggest that there is an overall minimal absorption from the lidocaine patch. However, the application of a depilatory agent leads to a more rapid and increased absorption of lidocaine.
A sensitive method for the quantification of lidocaine and its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), in animal plasma using high-performance liquid chromatography combined with electrospray ionization mass spectrometry is described. The sample preparation includes a liquid-liquid extraction with methyl tert-butylmethyl ether after addition of 2 M sodium hydroxide. Ethylmethylglycinexylidide (EMGX) is used as an internal standard. For chromatographic separation, an ODS Hypersil column was used. Isocratic elution was achieved with 0.01 M ammonium acetate and acetonitrile as mobile phases. Good linearity was observed in the range of 2.5-1000 ng ml −1 for lidocaine in both dog and horse plasma. For MEGX, linear calibration curves were obtained in the range of 5-1000 ng ml −1 and 20-1000 ng ml −1 for dog and horse plasma, respectively. In dog and horse plasma good linearity was observed in the range of 200-1500 ng ml −1 for GX. The limit of quantification (LOQ) in dog plasma for lidocaine, MEGX and GX was set at 2.5 ng ml −1 , 20 ng ml −1 and 200 ng ml −1 , respectively. For horse plasma a limit of quantification of 2.5 ng ml −1 , 5 ng ml −1 and 200 ng ml −1 was achieved for lidocaine, MEGX and GX, respectively. In dog plasma, the limit of detection (LOD) was found to be 0.8 ng ml −1 , 2.3 ng ml −1 and 55 ng ml −1 for lidocaine, MEGX and GX, respectively. In horse plasma the LOD's found for lidocaine, MEGX and GX, were 1.1 ng ml −1 , 0.5 ng ml −1 and 13 ng ml −1 , respectively. The method was shown to be of use in pharmacokinetic studies after application of a transdermal patch in dogs and after an intravenous infusion in horses.
This paper reports the surgical treatment of a tibial fracture in a castrated adult male Belgian Landrace pig of 180 kg. The fracture was repaired using an intramedullary Steinmann pin, combined with cerclage wire and external transfixation. In contrast to other animal species, the fracture repair in the pig was hindered by the short and curved bones, the thick subcutaneous fat layer and the pronounced musculature. Postoperatively, the pig developed an osteomyelitis of the tibia due to pin tract contamination. Despite this complication, the fracture healed acceptably when all fixation material was removed two months after surgery. The infection resolved quickly and a satisfactory clinical result was obtained.
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