Pharmacokinetics and safety profile of a novel progesterone aqueous formulation administered by the s.c. route

Abstract

A novel aqueous progesterone formulation was developed. Study I: Three-way cross-over, open-label study in 24 post-menopausal women. Comparison of the pharmacokinetic profiles of a single 100 mg dose of test product administered by subcutaneous (s.c.) and intramuscular (i.m.) injection and an i.m. reference oily product. Study II: Three-way cross-over open-label study of 25, 50 and 100 mg s.c. single doses of the aqueous formulation in 12 post-menopausal women. Study III: Parallel-group, observer-blinded study in 25 fertile women administered multiple s.c. 25 and 50 mg doses of the aqueous formulation once daily for 11 days. Baseline-corrected pharmacokinetic parameters were evaluated. Aqueous formulation (100 mg) was promptly absorbed, achieving progesterone peak serum levels at an earlier time than the reference (1 h vs. 7 h; p < 0.0001). Test and reference were bioequivalent in the extent of exposure: confidence intervals for AUC_0-t geometric means ratios were within the pre-specified 80–125% limits. Pharmacokinetics was linear over the range of doses studied. Steady state was reached within 4 days of multiple dose treatment. All treatments were well tolerated. Considering the advantages given by the possibility of self-medication, the s.c. aqueous formulation could offer a convenient alternative for patients on assisted reproductive technology treatments.

Keywords::

• Hormone replacement therapy
• infertility
• pregnancy

Acknowledgments

The authors acknowledge the collaboration of Dr. A. Rusca, CROSS Research S.A., Mendrisio, Switzerland and Prof. Markus Müller, Department of Clinical Pharmacology, Medical University of Vienna, Austria. We also thank Daniela Binelli for the statistical analyses and Analytisch Biochemisch Laboratorium BV, The Netherlands, for progesterone determination. These studies were funded by IBSA Institut Biochimique S.A., Switzerland.

Declaration of Interest: B. C. is an employee of IBSA Institut Biochimique S.A., all the other authors report no conflict of interest.