Comparative plasma dispositions of meloxicam and carprofen following oral administration in dogs
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Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used extensively in several domestic animal species for the treatment of a range of musculo-skeletal disorders and soft tissue injuries or inflammatory conditions. These drugs have antipyretic, anti-inflammatory and analgesic properties. Meloksikam (MLX) and carprofen (CRP) are two of the NSAIDs most commonly used by oral administration, which is the preferred route for the treatment of chronic pain and inflammation in dogs. The aim of the present study was to determine the pharmacokinetic properties of CRP and MLX in healthy dogs following oral administration at the doses of 2 mg/kg and 0.2 mg/kg bodyweight, respectively. Materials, Methods & Results: A total of 12 client-owned, cross-bred bitches, 2-5 years old and weighing 15-20 kg were used in the study. The animals were allocated into two groups of six such that the mean weight of animals in each group was similar. In Group I, CRP was given orally at a dose of 2 mg/kg and in Group II, MLX was given orally at a dose of 0.2 mg/kg. Blood samples were collected one day prior to drug administration and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 32, 40, 48, 56, 72 and 96 h post-treatment. Samples were centrifuged at 3000 g for 20 min and plasma was transferred to plastic tubes. Heparinized drug-free blood samples for analytical method development and validation process were collected from dogs not included in the study. All the plasma samples were stored at -20 degrees C until estimation of drug concentrations with all analyses completed within one month of sampling and they were analysed by high-performance liquid chromatography (HPLC). The terminal half-life of MLX (t(1/2) = 37.91 +/- 9.15 h) was significantly longer compared with that of CRP (t(1/2) = 17.02 +/- 6.95 h). In addition, CRP was absorbed faster (t(max) = 2.20 h) from gastrointestinal system and reached the peak plasma concentration significantly earlier than MLX (t(max) = 5.00 h). Moreover, the results indicated that Cmax (1.31 +/- 0.33 mu g/mL) and AUC (33.73 +/- 15.25 mu g.h/mL) for CRP values were significantly higher and larger compared with those observed for MLX (C-max = 0.39 +/- 0.13 mu g/mL and AUC = 17.99 +/- 4.97 mu g.h/mL), respectively following dose-proportionality comparisons for C max and AUC values of both molecules done after dose normalization. Discussion: The pharmacokinetic parameters of CPR were significantly different from those of MLX following oral administration. The results of the present study suggest that, although the systemic availability of CPR was higher, its absorption and elimination phases were significantly faster compared with those of MLX. Though, as the earlier and higher C max of CRP than MLX suggests that CRP seems to display anti-inflammatory effect faster than MLX in the treatment of the acute inflammatory disorders in dogs following oral administration, the anti-inflammatory effect is not necessarily directly related only to C max and t max, especially when the pharmacodynamic characteristics of the drugs may be different. The present study indicates that there are significant differences between pharmacokinetic parameters of MLX and CRP after oral administration in dogs. Because of the relatively slow absorption from gastrointestinal system after oral administration, MLX should be given intramuscular or subcutaneous routes in acute cases with respect of the time for onset of action.