Pharmacokinetics of progesterone in postmenopausal women: 1. Pharmacokinetics following intravaginal administration. 1998

C Mircioiu, and A Perju, and A Neagu, and E Griu, and G Calin, and D S Miron
Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

Progesterone was administered to postmenopausal women in a form of vaginal suppositories containing 100 and 200 mg active substance in Butyrum cacao (BC) and Massa estarinum (ME), a base with emulsifying properties. In the case of single doses, blood samples were taken at 2, 4, 6, 24, 48 and 72 h. Another group of patients received vaginal suppositories (100 mg progesterone) once a day for a 6 day period, with blood samples taken 12 h after each administration. The plasma levels of progesterone were evaluated by radioimmunoassay. The time of maximum concentration (tmax) was 4 h in most cases, and 6 h in the others. The plasma levels were not dose-proportional. Peak plasma concentrations were in the range of 10-15 ng/ml with a mean of 10.5 ng/ml for the 100 mg and 12 ng/ml for the 200 mg doses. The ratio of the mean area under the curve (AUC) for 200 mg and the mean AUC for the 100 mg dose was found to be 1.37. Replacing BC with ME resulted in the lowering of cmax and AUC, and an increase in tmax following a reducing in the rate and extent of adsorption. In the case of ME suppositories, the variability in AUC, cmax and tmax was greater compared to that observed with the BC suppositories. Elimination half-time was in the range of 9-10 h for BC and 14 h for ME suppositories. In vitro assessment of the release kinetics from a hydrophobic and an emulsion type base confirmed previous findings: the latter base assured better pharmaceutical availability. The repeated doses did not seem to produce an accumulation of progesterone in the plasma. On the contrary, a small decrease in plasma levels over time appeared during the 6 day period. Numerical analysis revealed an excellent goodness of fit for the in vivo experimental data via biexponential curves, i.e. a pseudomonocompartmental model.

UI MeSH Term Description Entries
D008657 Metabolic Clearance Rate Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site. Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D011374 Progesterone The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS. Pregnenedione,Progesterone, (13 alpha,17 alpha)-(+-)-Isomer,Progesterone, (17 alpha)-Isomer,Progesterone, (9 beta,10 alpha)-Isomer
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004655 Emulsions Colloids formed by the combination of two immiscible liquids such as oil and water. Lipid-in-water emulsions are usually liquid, like milk or lotion. Water-in-lipid emulsions tend to be creams. The formation of emulsions may be aided by amphiphatic molecules that surround one component of the system to form MICELLES. Emulsion
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000282 Administration, Intravaginal The insertion of drugs into the vagina to treat local infections, neoplasms, or to induce labor. The dosage forms may include medicated pessaries, irrigation fluids, and suppositories. Administration, Vaginal,Drug Administration, Vaginal,Instillation, Vaginal,Intravaginal Administration,Vaginal Drug Administration,Vaginal Administration,Administration, Vaginal Drug,Administrations, Intravaginal,Administrations, Vaginal,Administrations, Vaginal Drug,Drug Administrations, Vaginal,Instillations, Vaginal,Intravaginal Administrations,Vaginal Administrations,Vaginal Drug Administrations,Vaginal Instillation,Vaginal Instillations
D001682 Biological Availability The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action. Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities
D013223 Statistics as Topic Works about the science and art of collecting, summarizing, and analyzing data that are subject to random variation. Area Analysis,Estimation Technics,Estimation Techniques,Indirect Estimation Technics,Indirect Estimation Techniques,Multiple Classification Analysis,Service Statistics,Statistical Study,Statistics, Service,Tables and Charts as Topic,Analyses, Area,Analyses, Multiple Classification,Area Analyses,Classification Analyses, Multiple,Classification Analysis, Multiple,Estimation Technic, Indirect,Estimation Technics, Indirect,Estimation Technique,Estimation Technique, Indirect,Estimation Techniques, Indirect,Indirect Estimation Technic,Indirect Estimation Technique,Multiple Classification Analyses,Statistical Studies,Studies, Statistical,Study, Statistical,Technic, Indirect Estimation,Technics, Estimation,Technics, Indirect Estimation,Technique, Estimation,Technique, Indirect Estimation,Techniques, Estimation,Techniques, Indirect Estimation

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