Tese
Avaliação farmacocinética, hematológica e espermática de pôneis tratados com meloxicam
Fecha
2010-07-15Registro en:
POZZOBON, Ricardo. PHARMACOKINETICS, HEMATOLOGICAL AND SPERMATIC
PARAMETERS IN PONIES TREATED WITH MELOXICAM. 2010. 88 f. Tese (Doutorado em Medicina Veterinária) - Universidade Federal de Santa Maria, Santa Maria, 2010.
Autor
Pozzobon, Ricardo
Institución
Resumen
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.