Compositions and methods for delaying the incidence of labor
The invention provides compositions and methods for delaying the onset of delivery in a pregnant subject, such as a pregnant human subject, that is undergoing or at risk of undergoing preterm labor at a gestational age of from about 24 weeks to about 34 weeks. Using the compositions and methods described herein, such subjects may be administered nifedipine in combination with a prostaglandin F2α (PGF2α) antagonist. Exemplary PGF2α receptor antagonists that may be used for the treatment or prevention of preterm labor as described herein include 1,3-thiazolidine-2-carboxamide compounds, such as (3S)-3-({[(2S)-3-(biphenyl-4-ylsulfonyl)-1,3-thiazolidin-2-yl]carbonyl}-amino)-3-(4-fluorophenyl)propyl L-valinate or a pharmaceutically acceptable salt thereof (e.g., (3S)-3-({[(2S)-3-(biphenyl-4-ylsulfonyl)-1,3-thiazolidin-2-yl]carbonyl}-amino)-3-(4-fluorophenyl)propyl L-valinate hydrochloride. Using the compositions and methods described herein, a subject may be dosed with a PGF2α receptor antagonist and a reduced amount or frequency of nifedipine relative to the amount or frequency of nifedipine that would otherwise be used if the nifedipine were given in the absence of the PGF2α receptor antagonist.
1. A method of delaying the onset of delivery in a pregnant human subject, the method comprising administering to the subject a therapeutically effective amount of a compound represented by formula (2)
or a pharmaceutically acceptable salt thereof,
and wherein the subject is further administered nifedipine in an amount of about 20 mg per dose.
2. A method of delaying the onset of delivery in a pregnant human subject, the method comprising administering to the subject a therapeutically effective amount of a compound represented by formula (2)
or a pharmaceutically acceptable salt thereof,
and wherein the subject is further administered nifedipine in an amount of about 20 mg in the first hour of treatment.
3. The method of claim 1 , wherein the compound is represented by formula (3)
4. The method of claim 1 , wherein the nifedipine is administered to the subject in one or more doses per 12 hours, 24 hours, 48 hours, or week.
5. The method of claim 4 , wherein a dose of the nifedipine is administered to the subject once every 4 to 12 hours.
6. The method of claim 1 , wherein the nifedipine is periodically administered to the subject until the subject reaches a gestational age of at least about 34 weeks.
7. The method of claim 6 , wherein the nifedipine is periodically administered to the subject until the subject reaches a gestational age of from about 34 weeks to about 40 weeks.
8. The method of claim 1 , wherein the nifedipine is administered to the subject orally.
9. The method of claim 1 , wherein the subject has a gestational age of from about 24 weeks to about 36 weeks prior to administration of the nifedipine and the compound to the subject.
10. The method of claim 1 , wherein the subject exhibits four or more uterine contractions per 30 minutes prior to administration of the nifedipine and the compound to the subject.
11. The method of claim 2 , wherein the compound is represented by formula (3)