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-Iscove sco, Paris, France) and to compare the bioavailability of intramuscula r versus oral routes of administration. Design: Prospective, randomize d, open label crossover protocol with 7 days between dosages. Setting: Academic institution. Participants: Fifteen normal postmenopausal wom en. Interventions: All subjects participated in three separate protoco ls: [1] micronized P (200 mg) or placebo under fasting or nonfasting c onditions 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 fo r 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 (C(max)) without affecting time to maxi mum serum concentration (T(max)) (P < 0.05). Micronized P absorption a nd elimination were first-order processes and exhibited dose-independe nt pharmacokinetics between 100 and 300 mg. After intramuscular P, C(m ax) was higher and T(max) occurred later compared with the oral P prep aration. Oral P had lower relative bioavailability (8.6%) than intramu scular P. Conclusions: Absorption of micronized P was enhanced twofold in the presence of food. Both absorption and elimination were dose-in dependent, dose proportionality being confirmed. Bioavailability of th e oral P was approximately 10% compared with intramuscular P.