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1. Weekly intramuscular injections of (250 mg/week) of 17-hydroxyprogesterone caproate (17-OHPC) are the only treatment option for prevention of preterm birth in women with a prior history of preterm delivery. 2. The objective of the current study was to evaluate the use of an alternate formulation and the feasibility of an alternate route of administration of this agent. 17-OHPC was administered to adult female SD rats, as marketed oily formulation intramuscularly, or as a solution IV, IM, or PO. 3. Plasma concentrations of 17-OHPC were measured by LC-MS-MS and pharmacokinetic parameters were calculated by non-compartmental analysis, using WinNonLin (Certara, St. Louis, MO). 4. After IV or IM administration as a solution, the mean half-life of 17-OHPC was around 11 h. The bioavailability was nearly 100% after IM administration, but was very low (3%) after PO administration of a solution dosage form. 5. Intramuscular injection of the oily formulation resulted in low levels of 17-OHPC that were sustained for a prolonged time period with a projected bioavailability close to 100%. 6. The pharmacokinetics of 17-OHPC is dependent on the formulation and the route of administration. 7. The low bioavailability after oral administration indicates that oral administration of 17-OHPC may not be feasible with simple formulations of this drug.

To compare rates of preterm birth before 35 weeks based on cervical length measurement at 16-20 weeks in women with twin gestations who received 17-α hydroxyprogesterone caproate (17OHPC) or placebo.This is a secondary analysis of a randomised, double-blind, placebo-controlled trial of twin gestations exposed to 17OHPC or placebo. Baseline transvaginal ultrasound evaluation of cervical length was performed prior to treatment assignment at 16-20 weeks. Cervical length measurements were categorised according to the 10th, 25th, 50th and 75th percentiles in the women studied. The effect of 17OHPC administration in women with a short (25th percentile) and long (75th percentile) cervix was evaluated.Of 661 twin gestations studied, 221 (33.4%) women enrolled at 11 centers underwent cervical length measurement. The 10th, 25th, 50th, 75th percentiles for cervical length at 16-20 weeks were 32, 36, 40 and 44 mm, respectively. The risk of preterm birth35 weeks was increased in women with a cervical length25th percentile (55.8 vs. 36.9%, p=0.02). However, a cervical length75th percentile at this gestational age interval was not protective for preterm birth (36.5 vs. 42.9%, p=0.42). Administration of 17OHPC did not reduce preterm birth before 35 weeks among those with either a short or a long cervix (64.3 vs. 45.8%, p=0.18 and 38.1 vs. 35.5%, p=0.85, respectively).Women with twin gestations and a cervical length below the 25th percentile at 16-20 weeks had higher rates of preterm birth. In this subgroup of women, 17 OHPC did not prevent preterm birth before 35 weeks gestation. A cervical length above the 75th percentile at 16-20 weeks did not significantly reduce the risk of preterm birth in this high risk population.

Electrodeposited nanocrystalline Co offers a relatively unique opportunity to study the interaction of two fundamentally different elementary solid state reactions: grain growth and e (HCP) to α (FCC) allotropic phase transformation. Samples were isothermally annealed at temperatures above and below the equilibrium transformation temperature (Teα = 695 K) and quenched to ambient for subsequent characterization by X-ray diffraction (XRD) and transmission electron microscopy (TEM). Isothermal annealing above 695 K resulted in concurrent grain growth and e to α transformation. Unexpectedly, however, simultaneous grain growth and e to α transformation also occurred during isothermal annealing at temperatures as low as 573 K, i.e. 122 K below the expected equilibrium Teα. It was observed that non-equilibrium α-Co formed within a matrix of nanocrystalline e-Co via abnormal grain growth, and is therefore fundamentally different from the e to α transformation typically observed in conventional polycrystalline Co.

The aim of this study was to determine if magnesium sulfate has a direct inhihitory effect in vivo on oxytocin-induced myometnal contractility. We used 13 preterm non-laboring sheep to evaluate the ability of magnesium sulfate to inhibit oxytocin-induced contractions. In each of seven animals, we achieved three sequential steady state concentrations of magnesium (3.5, 5.5, and 8.3 mEq/L). A bolus of oxytocin was given before magnesium infusion and after 140 min at each steady state concentration. The myometrial response to each oxytocin injection was quantified. In six other animals, we infused magnesium sulfate over 24 h and achieved an average concentration of 7.7 mEq/L. Oxytocin boluses were given after 4 and 24 h of magnesium infusion and the myometrial response was quantified. Magnesium sulfate did not significantly reduce oxytocin-induced contractility with either short (2 h) or prolonged (24 h) infusion. There was no dose related contraction inhibition by magnesium sulfate over concentrations rangi...

We evaluated in pregnant sheep the effectiveness of nicardipine, a calcium channel blocker, in inhibiting and maintaining inhibition of oxytocin-induced myometrial contractility over a 24-hr period. We also evaluated the effect of this agent on the myometrial β-adrenergic receptor cascade and oxytocin receptors. We placed catheters into the maternal aorta, inferior vena cava and amnionic cavity and obtained a myometrial biopsy from 5 near term pregnant sheep. After 1–4 days of recovery, we infused nicardipine intravenously at a rate of 4 μg/kg/min for 24 hrs. Animals received the same bolus injection of oxytocin into the aorta prior to and after 4 and 24 hr of nicardipine infusion. We quantified the uterine response to oxytocin by measuring the area under the uterine pressure-time curve with planimetry. After 24 hr infusion of nicardipine, the animals were sacrificed and another myometrial biopsy was obtained. Nicardipine concentrations neared steady state concentration by 4 hr averaging 61 ± 23 ng/ml. Ox...

In this article, we will review the pharmacokinetics and pharmacology of the most frequently used labor inhibiting agents with a view toward optimizing efficacy and minimizing adverse side effects.