OBJECTIVE: Oxytocin antagonists maybe useful in inhibiting the uterine contractions of preterm labor. One such compound is TT-235. The purpose of this study was to compare the resistance of TT-235 and oxytocin to enzymatic degradation by oxytocinase in pregnant human. METHODS: Blood samples from pregnant women not in labor were incubated in vitro with known amounts of oxytocin and TT-235. Samples were collected at 0, 15, 30, 45 and 60 minute intervals for oxytocin analysis and at 0, 10, 60 and 360 minutes for TT-235 analysis. Oxytocin was analyzed by radioimmunoassay after extraction while TT-235 was analyzed by radioreceptor assay. RESULTS: In human blood, oxytocin was readily metabolized with greater than 83% disappearance over the 60 minute incubation period. In contrast, TT-235 was stable up to 360 minutes of incubation. CONCLUSION: This study suggests that: (1) blood from pregnant human does contain oxytocinase at least in vitro; and (2) TT-235 was resistant to enzymatic degradation by human blood, implying that this oxytocin antagonist may have prolonged activity in vivo in humans.
Cystinyl Aminopeptidase ; Female ; Humans ; Metabolism* ; Obstetric Labor, Premature ; Oxytocin* ; Plasma* ; Pregnancy ; Pregnant Women* ; Radioimmunoassay ; Radioligand Assay ; Uterine Contraction ; Uterus

Gestational diabetes insipidus, which occurs rarely during late pregnancy, may injure the mother and fetus neurologically. It takes place in about 4 of every 100,000 pregnancies. Increased placental-derived vasopressinase in late pregnancy markedly degrades vasopressin. The decreased vasopressin activity causes hypotonic polyuria, polydipsia, and dehydration. We report a woman with gestational diabetes insipidus who had no abnormal laboratory tests before developing symptoms. The diabetes insipidus was controlled well by administering nasal desmopressin (1.desamino.8.D.arginine vasopressin, DDAVP) followed by resolution of the signs and symptoms after delivery. Although gestational diabetes insipidus is rare, a prompt diagnosis and appropriate treatment to reduce the risks of maternal and fetal injury are important.
Cystinyl Aminopeptidase ; Deamino Arginine Vasopressin ; Dehydration ; Diabetes Insipidus ; Diabetes, Gestational ; Female ; Fetus ; Humans ; Hypogonadism ; Mitochondrial Diseases ; Mothers ; Ophthalmoplegia ; Polydipsia ; Polyuria ; Pregnancy ; Pregnancy Trimester, Third ; Vasopressins