Abstract:
To determine the intercyclic effect of oxytocin and carbetocin on equine myometrial tissue, the effect of the drugs was
evaluated through pharmacokinetic and pharmacodynamic studies. The complete pharmacokinetic profile for oxytocin was
unknown and had to be established. To do so, 25 IU of oxytocin were administered intravenously to six cycling mares and blood
samples were collected before and 2, 4, 8, and 15 min after administration. The half-life of oxytocin was determined to be 5.89
min, the clearance rate 11.67 L/min, mean residence time (MRT) 7.78 min. The effective plasma concentration was estimated to
be 0.25 ng/mL. This was similar to the concentration achieved for the organ bath study where the concentration that produced 50%
of the maximum effect (EC50) was calculated at 0.45 ng/mL. To determine the intercyclic effect of oxytocin and carbetocin uterine
myometrial samples were collected from slaughtered mares in estrus, diestrus, and anestrus. The samples were mounted in organ
baths and exposed to four ascending, cumulative doses of oxytocin and carbetocin. Area under the curve and amplitude, maximum
response (Emax), and concentration that produced 50% of the maximum effect were studied for each agonist and statistically
evaluated. The effect of oxytocin on equine myometrial tissue was higher during diestrus, and surprisingly anestrus, than during
estrus, whereas the effect of carbetocin was the same independent of the stage of estrous cycle. A significant difference was found
for estrous and anestrous samples when oxytocin was used but not when carbetocin was used.
