Avaliação farmacocinética, hematológica e espermática de pôneis tratados com meloxicam

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most used drugs in veterinary medicine. Most of the original NSAIDs inhibit primarily cyclooxygenase-1 (COX-1) and cause adverse effects such as gastrointestinal ulcers, kidney and liver damage. When the formerly supposed anti-inflammatory COX-2 enzyme was discovered, NSAIDs were developed to selectively inhibit this enzyme. Today it is known that COX-2 is not exclusively expressed in inflammatory conditions; it also has physiologic functions in tissues such as brain, male and female reproductive tracts. Several horses, such as stallions, are treated with some NSAID, and many times these treatments are prolonged as in osteoarthritis and laminitis. In horses, there is still little information about the effects of COX-1 and COX-2 selective NSAIDs on the reproductive and cardiovascular systems. Pharmacokinetic information of NSAIDs, like meloxicam, in different health conditions and horse breeds may explain differences in efficiency and/or toxicity. This study evaluated meloxicam pharmacokinetics on 3 groups with 3 animals each: a group of ponies with induced synovitis, a group of healthy ponies and a group of healthy horses. All animals were treated with the recommended dosage (0.06 mg/kg, PO) of meloxicam. Plasma was obtained from blood samples collected before (time 0), 15 and 30 minutes, and 1, 2, 4, 8, 12 and 24 hours after medication. The time to reach the maximum plasma concentration (Tmax) was longest (P<0.05) in horses and the maximum concentration (Cmax) was highest (P<0.05) in healthy ponies. The initial plasma concentrations were achieved more quickly (P<0.05) in both ponies groups. In a second study, the effect of meloxicam (preferential COX-2 NSAID) and ketoprofen (unspecific NSAID) was evaluated on hematological and biochemical variables, on the gastric mucosa and on semen quality of 6 healthy pony stallions. The ponies were treated for 30 days and then the experiment was repeated a second time changing the ponies group in a latin square design. The stallions were distributed equally into 3 groups; one was treated with meloxicam (0.6 mg/kg oral administration, PO; n=6), another with ketoprofen (2.2 mg/kg, PO; n=6, positive control) and the negative control group (n=6) received no treatment. Blood samples were obtained once a week for six weeks, beginning before treatment and extending until 1 week after the treatment ended to evaluate hematologic, coagulation and biochemical (AP, AST and GGT) profiles. Gastroscopic evaluation was determined 1 week before and 1 week after the treatment ended. Semen was collected and evaluated twice a week for 16 weeks: before treatment began (week 0), during 4 weeks of treatment (weeks 1-4), and 10 weeks after the treatment ended (weeks 5-15). Concentration of total prostaglandins (PGs) was measured in the seminal plasma of ejaculates collected before (week 0), during (1 to 4 weeks) and after treatment (week 5 and week 15). The treatments did not alter any evaluated hematological and biochemical parameter as well as on the gastric mucosa, but there was a time effect on fibrinogen, pro-thrombin time and activated partial thromboplastin time. Meloxicam treatment caused more (P<0.05) damage to the sperm membrane integrity and decreased (P<0.05) membrane function and total PGs concentration. A significant increase (P<0.05) in tail defects also was observed 2 weeks after treatment ended. In summary, pharmacokinetics differed between healthy ponies and those with synovitis. This may be the result of drug migration to the injury site. Meloxicam absorption was faster in ponies. No influence of the treatments was observed on the hematological or biochemical parameters as well as on gastric mucosa. Thirty day long meloxicam treatment lowered PGs in seminal plasma and affected semen quality. This suggests a physiological function of COX-2 in the stallion s reproductive tract.