Objectives: 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.
Design: Prospective, randomized, open label crossover protocol with 7 days between dosages.
Setting: Academic institution.
Participants: Fifteen normal postmenopausal women.
Interventions: All subjects participated in three separate protocols:  micronized P (200 mg) or placebo under fasting or nonfasting conditions once daily for 5 days;  micronized P (100, 200, or 300 mg) once daily under fasting conditions for 5 days; and  micronized P (200 mg) or intramuscular P (50 mg in oil) administered once daily for 2 days.
Main outcome measures: Serum P concentrations were measured in all groups.
Results: 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.
Conclusions: 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.