The absorption of oral micronized progesterone: the effect of food, dose proportionality, and comparison with intramuscular progesterone*†

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 7days between dosages. Setting Academic institution. Participants Fifteen normal postmenopausal women. Interventions All subjects participated in three separate protocols: [1] micronized P (200mg) or placebo under fasting or nonfasting conditions once daily for 5days; [2] micronized P (100, 200, or 300mg) once daily under fasting conditions for 5days; and [3] micronized P (200mg) or intramuscular P (50mg in oil) administered once daily for 2days. 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 (AUC 0 to 24 ) and the maximum serum P concentration (C max ) without affecting time to maximum serum concentration (T max ) ( P max was higher and T max 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.