title: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Sator
authors.forename: Milko
authors.initials: M
authors.lastname: Radicioni
authors.forename: Barbara
authors.initials: B
authors.lastname: Cometti
authors.forename: Luca
authors.initials: L
authors.lastname: Loprete
authors.forename: Chiara
authors.initials: C
authors.lastname: Leuratti
authors.forename: Doreen
authors.initials: D
authors.lastname: Schmidl
authors.forename: Gerhard
authors.initials: G
authors.lastname: Garhöfer
mesh_terms: D000042:Absorption; D000293:Adolescent; D000328:Adult; D000368:Aged; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008875:Middle Aged; D017698:Postmenopause; D017697:Premenopause; D011374:Progesterone / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D005300:Fertility Agents, Female; D011374:Progesterone