Effect of formulation and route of administration on the distribution of 17-hydroxyprogesterone caproate in rats

Abstract

1. Weekly intramuscular (250 mg/week) or subcutaneous (275 mg/week) injections of 17-hydroxyprogesterone caproate (17-OHPC) is the only treatment option for the prevention of preterm birth in women with a prior history of preterm delivery.

2. The objective of the current study was to determine the relative distribution of 17-OHPC in selected tissues in adult female SD rats after IM (oily formulation or solution), IV (solution), PO (solution), or intravaginal (suppository) administration.

3. Plasma, uterus, adipose, and liver samples were collected at various times and analysed by LC-MS-MS.

4. The highest concentrations of 17-OHPC were observed in the adipose tissue, after IM (oily formulation), and intravaginal administration.

5. Substantial concentrations of 17-OHPC were also observed in the uterus after IM, intravaginal and IV administration.

6. 17-OHPC was not detected in the liver and in any of the tissues tested after PO administration.

7. 17-OHPC levels in plasma after intravaginal suppository administration were low despite substantial concentrations in the adipose and the uterus.

8. The distribution of 17-OHPC depends on the formulation, the route of administration, and the sampling time.

9. Low systemic concentrations and substantial distribution in the tissues of interest after intravaginal administration warrants future studies to evaluate the potential of the daily intravaginal route of administration of 17-OHPC.

Keywords:

• Preterm birth
• 17-hydroxyprogestrone caproate
• adipose
• uterus
• distribution

Disclosure statement

The authors report no declarations of interest.

Data availability statement

Data is available upon reasonable request to corresponding author/s.

Additional information

Funding

This research was supported in part by the Obstetric-Foetal Pharmacology Research Unit Network Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD-047905-2].