The pharmacokinetics of the oxytocin antagonist atosiban in pregnant women with preterm uterine contractions.
OBJECTIVE
Our purpose was to evaluate the pharmacokinetics of atosiban, an oxytocin antagonist, during and after intravenous infusion in pregnant patients having at least six contractions per hour. The relationship between atosiban infusion and uterine activity was also assessed.


METHODS
Plasma samples from eight pregnant patients treated with intravenous atosiban (300 micrograms/min for 6 to 12 hours) were analyzed for atosiban concentration by a specific radioimmunoassay procedure. Contraction rate data were obtained by external tocodynamometry for 1 hour before the infusion and during the subsequent infusion.


RESULTS
The average steady-state plasma concentrations of patients receiving intravenous atosiban were 442 +/- 73 ng/ml (mean +/- SD), with steady state achieved by 1 hour after the start of the infusion. After the completion of the infusion, plasma concentrations declined rapidly in a biexponential manner with initial and terminal half-life estimates of 13 +/- 3 and 102 +/- 18 minutes, respectively. The effective half-life was 18 +/- 3 minutes. The plasma clearance of atosiban was relatively high (42 L/hr) and the volume of distribution (approximately 18 L) was consistent with distribution into extracellular fluid. Of the seven patients evaluated for uterine activity, the mean contraction rate decreased by 75% during the third hour of treatment and remained low until treatment termination.


CONCLUSIONS
On the basis of earlier published reports, the pharmacokinetics of atosiban in pregnant patients are similar to those in nonpregnant women. Although the patient population was small, a consistent reduction in uterine activity was observed during atosiban infusion.
Goodwin
T M
TM
Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, USA.
Millar
L
L
North
L
L
Abrams
L S
LS
Weglein
R C
RC
Holland
M L
ML
D005260:Female; D006207:Half-Life; D006727:Hormone Antagonists / Q000493:pharmacokinetics*; D006801:Humans; D007700:Kinetics; D008657:Metabolic Clearance Rate; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D010121:Oxytocin / Q000037:antagonists & inhibitors*; D011247:Pregnancy; D015149:Tocolytic Agents / Q000493:pharmacokinetics*; D014590:Uterine Contraction / Q000187:drug effects*; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
D006727:Hormone Antagonists; D015149:Tocolytic Agents; C047046:atosiban; D010121:Oxytocin; D014668:Vasotocin