Pharmacokinetic properties of the tocolytic agent [Mpa1, D-Tyr(Et)2, Thr4, Orn8]-oxytocin (antocin) in healthy volunteers.

ABSTRACT

OBJECTIVE: The aim of this study was to study the pharmacokinetics of antocin, the tocolytic oxytocin antagonist [Mpa1, D-Tyr2(Et), Thr4, Orn8]-oxytocin. DESIGN: Antocin was injected intravenously as a bolus dose (5 mumol). Blood samples were taken at intervals for 240 minutes. In addition, the binding of 125I-Tyr10-antocin to blood constituents was determined and compared with 125I-AVP and 125I-[Mpa1, D-Arg8]-vasopressin (desmopressin). SUBJECTS: Eight healthy, non-smoking adults, three male and five female. MEASUREMENTS Antocin was measured using a specific radioimmunoassay after prior extraction of the plasma. Plasma binding was estimated using polyethyleneglycol precipitation. RESULTS: The rate of plasma disappearance of antocin was best fitted by a biexponential curve. The clearance of antocin was 23.5 +/- 7.6 l/h, the volume of distribution was 13.1 +/- 3.8 l and the biological half-life was 39.0 +/- 4.1 minutes. A greater proportion of 125I-Tyr10-antocin bound to plasma proteins (33.5%) and red blood cells (13%) than did 125I-AVP, 125I-desmopressin and unlabelled desmopressin. CONCLUSIONS: The half-life was longer and the clearance of antocin was less than that found in a previous study when a non-specific antiserum was used. This is most likely because of the extended blood sampling time period which revealed the biphasic decay pattern. The higher plasma clearance of antocin compared to oxytocin and desmopressin may be explained by its increased binding to blood constituents rather than by differences in enzymatic degradation of the molecules.