Atosiban, an oxytocin receptor blocking agent: pharmacokinetics and inhibition of milk ejection in dairy cows.

Plasma concentrations of the oxytocin receptor blocking agent Atosiban were measured at 2, 4, 10, 15 and 20 min after injection of 5, 10, 20 and 50 micrograms Atosiban/kg body weight in six dairy cows. The half life of Atosiban was 18 min and the total body clearance was 3301 ml/min. Intramammary pressure (IMP) within the teat cistern was measured in six cows before and after i.v. injection of 0 or 20 micrograms Atosiban/kg body weight and repeated injections of 0.2 or 0.5 i.u. oxytocin. IMP was also measured in eleven cows after injection of 0, 10 or 50 micrograms Atosiban/kg body weight: in seven during oxytocin infusions, in four after oxytocin injections in successively increasing dosages (0.05, 0.1, 0.2, 0.5, 1 and 10 i.u.). The occurrence of milk ejection was indicated by a rise in IMP. After injection of 20 micrograms Atosiban/kg body weight, 0.2 i.u. oxytocin did not induce an IMP rise before 48 min, whereas 0.5 i.u. oxytocin induced an IMP rise within 4 min. The time from the start of infusion until the beginning of the IMP rise and the duration of IMP rise during oxytocin infusions both increased, whereas the IMP rise itself was diminished by increasing Atosiban dosages. The amount of injected oxytocin necessary to induce an IMP response increased with increasing Atosiban dosages. Atosiban was shown to have a powerful effect in inhibiting milk ejection in dairy cows.