PHARMACOKINETIC PROPERTIES OF THE TOCOLYTIC AGENT [MPA(1), D-TYR(ET)(2), THR(4), ORN(8)]-OXYTOCIN (ANTOCIN) IN HEALTHY-VOLUNTEERS

OBJECTIVE The aim of this study was to study the pharmacokinetics of a ntocin, the tocolytic oxytocin antagonist [Mpa1, D-Tyr2(Et), Thr4, Orn 8]-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 I-125-Tyr10-antocin to blood constituents was determined and compared with I-125-AVP and I-125-[Mpa1, D-Arg8]-vasop ressin (desmopressin). SUBJECTS Eight healthy, non-smoking adults, thr ee male and five female. MEASUREMENTS Antocin was measured using a spe cific radioimmunoassay after prior extraction of the plasma. Plasma bi nding was estimated using polyethyleneglycol precipitation. RESULTS Th e rate of plasma disappearance of antocin was best fitted by a biexpon ential 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 I-125-Tyr10-antocin bound to p lasma proteins (33.5%) and red blood cells (13%) than did I-125-AVP, I -125-desmopressin and unlabelled desmopressin. CONCLUSIONS The half-li fe 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 revea led the biphasic decay pattern. The higher plasma clearance of antocin compared to oxytocin and desmopressin may be explained by its increas ed binding to blood constituents rather than by differences in enzymat ic degradation of the molecules.