Pharmacokinetics and metabolism of orally administered firocoxib, a novel second generation coxib, in horses

The primary objective of this study was to determine the pharmacokinetic profile of firocoxib, a novel second generation coxib, in horses. Horses were administered either a single oral or intravenous dose of firocoxib at 0.1 mg/kg in a two-period crossover study with 12 animals. The dosage was based on previously determined pharmacodynamic parameters. Oral firocoxib was well absorbed with an average bioavailability (absolute) of 79% and a Cmax of 75 ng/mL at 3.9 h. The average elimination half-life was 30 h. Following intravenous administration the average Cmax was 210 ng/mL and the elimination half-life was 34 h. The area under the curve [AUC(0-tlast)] was 1.8 microg.h/mL for the oral dose and 2.3 microg.h/mL for the intravenous dose. Firocoxib was widely distributed with a volume of distribution value of 1.7 L/kg for the intravenous dose. Biotransformation of firocoxib was via dealkylation and glucuronidation to inactive metabolites, namely descyclopropylmethylfirocoxib and its glucuronide conjugate. Urinary excretion was the major route of elimination, and the clearance rate was 37 mL/h/kg.     

N. femoralis, N. obturatorius and N. ischiadicus: deviation in creation in the dogs

Two hundred and twelve dog cadavers belonging to different breeds were examined, to investigate the formation of the femoral, obturator and the sciatic nerve. Besides the commonly described formation patterns of the mentioned nerves, some variations were also found. These variations were not gender-related, but on the other hand we discovered a certain correlation between the variations appearing in the formation of the femoral, obturator and the sciatic nerve. In 74.05% of cases, the femoral nerve was formed from ventral branches of the 4th, 5th and 6th lumbar nerve, and 16.98% of the dogs had the nerve formed from ventral branches of the 3rd, 4th and 5th lumbar nerve. Many dogs (i.e. 2.30%) had the femoral nerve formed from the ventral branches of the 5th, 6th and 7th, the 3rd, 4th, 5th and 6th or the 4th, 5th, 6th and 7th lumbar nerve, respectively. In 1.88% of dogs in particular, the femoral nerve was formed from ventral rami of the 4th and 5th lumbar nerve. In 66.98% of the examined dogs, the obturator nerve was formed from the ventral branches of the 4th, 5th and 6th lumbar nerve, followed by 16.59% of the dogs with the obturator nerve formed from the ventral rami of the 4th and 5th lumbar nerve and 9.43% of dogs in which the nerve was formed from the ventral branches of the 5th and 6th lumbar nerve. In 4.71% of dogs, the obturator nerve was formed from the ventral rami of the 4th, 5th, 6th and 7th lumbar nerve, while only 2.30% of the examined dogs had the same nerve formed from the ventral branches of the 5th, 6th and 7th lumbar nerve. The sciatic nerve was formed from ventral branches of the 6th and 7th lumbar nerve and the 1st sacral nerve in 86.79% of the dogs. In 5.18% of cases, the same nerve was formed from a junction of the ventral branches of the 7th lumbar and the 1st and 2nd sacral nerve, and, in the same percentage of cases, it was formed from a junction of ventral branches of the 6th and 7th lumbar nerve and the 1st and 2nd sacral nerve. In 2.83% of the dogs, it was formed from a junction of the ventral branches of the 6th and 7th lumbar and the 1st sacral nerve. The correlation of variations established in the formation of the femoral, obturator and the sciatic nerve was not statistically significant.     

Affinity of detomidine, medetomidine and xylazine for alpha-2 adrenergic receptor subtypes

α₂-Adrenergic receptor agonists are widely used in veterinary medicine as sedative/hypnotic agents. Four pharmacological subtypes of the α₂-adrenergic receptor (A, B, C and D) have been identified based primarily on differences in affinity for several drugs. The purpose of this study was to examine the affinities of the sedative agents, xylazine, detomidine and medetomidine at the four α₂-adrenergic receptor subtypes. Saturation and inhibition binding curves were performed in membranes of tissues containing only one subtype of a₂-adrenergic receptor. The K_D for the α₂-adrenergic receptor radioligand, [³H]-MK-912, in HT29 cells (α_2A-), neonatal rat lung (α_2B-), OK cells (α_2C-) and PC12 cells transfected with RG20 (α_2D-) were 0.38 ± 0.08 n m , 0.70 ± 0.5 n m , 0.07 ± 0.02 n m and 0.87 ± 0.03 n m , respectively. Detomidine and medetomidine had approximately a 100 fold higher affinity for all the α₂-adrenergic receptors compared to xylazine but neither agonist displayed selectivity for the α₂-adrenergic receptor subtypes. These data suggest that available sedative/hypnotic α₂-adrenergic receptor agonists can not discriminate between the four known α₂-adrenergic receptor subtypes.