Fertility and Sterility, 60(1), 26-33
To examine the effects of food ingestion and administered dose on the absorption of oral micronized P (Utrogestan; Besins-Iscovesco, Paris, France) and to compare the bioavailability of intramuscular versus oral routes of administration.
Prospective, randomized, open label crossover protocol with 7 days between dosages.
Academic institution.
Fifteen normal postmenopausal women.
All subjects participated in three separate protocols: [1] micronized P (200 mg) or placebo under fasting or nonfasting conditions once daily for 5 days; [2] micronized P (100, 200, or 300 mg) once daily under fasting conditions for 5 days; and [3] micronized P (200 mg) or intramuscular P (50 mg in oil) administered once daily for 2 days.
Serum P concentrations were measured in all groups.
Concomitant food ingestion increased the area under the serum P concentration versus time curve (AUC0 to 24) and the maximum serum P concentration (Cmax) without affecting time to maximum serum concentration (Tmax) (P < 0.05). Micronized P absorption and elimination were first-order processes and exhibited dose-independent pharmacokinetics between 100 and 300 mg. After intramuscular P, Cmax was higher and Tmax occurred later compared with the oral P preparation. Oral P had lower relative bioavailability (8.6%) than intramuscular P.
Absorption of micronized P was enhanced twofold in the presence of food. Both absorption and elimination were dose-independent, dose proportionality being confirmed. Bioavailability of the oral P was approximately 10% compared with intramuscular P.
Simon, J. A., Robinson, D. E., Andrews, M. C., Hildebrand JR 3rd, Rocci ML Jr, Blake, R. E., & Hodgen, G. D. (1993). The absorption of oral micronized progesterone: the effect of food, dose proportionality, and comparison with intramuscular progesterone. *Fertility and sterility*, *60*(1), 26-33. https://doi.org/10.1016/s0015-0282(16)56031-2
Simon JA, Robinson DE, Andrews MC, Hildebrand JR 3rd, Rocci ML Jr, Blake RE, et al. The absorption of oral micronized progesterone: the effect of food, dose proportionality, and comparison with intramuscular progesterone. Fertil Steril. 1993;60(1):26-33. doi:10.1016/s0015-0282(16)56031-2
Simon, J. A., et al. "The absorption of oral micronized progesterone: the effect of food, dose proportionality, and comparison with intramuscular progesterone." *Fertility and sterility*, vol. 60, no. 1, 1993, pp. 26-33.
Administration, Oral, Adult, Aged, Biological Availability, Drug Compounding, Eating, Fasting/metabolism, Female, Half-Life, Humans, Injections, Intramuscular, Intestinal Absorption, Menopause/metabolism, Middle Aged, Progesterone/administration & Dosage/blood/pharmacokinetics, Prospective Studies, Progesterone,