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


METHODS
Prospective, randomized, open label crossover protocol with 7 days between dosages.


METHODS
Academic institution.


METHODS
Fifteen normal postmenopausal women.


METHODS
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.


METHODS
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.
Obstetrics and Gynecology, Georgetown University School of Medicine, Washington, D.C. 20007.
J A
JA
Simon
D E
DE
Robinson
M C
MC
Andrews
J R
JR
Hildebrand
M L
ML
Rocci
R E
RE
Blake
G D
GD
Hodgen
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001682:Biological Availability; D004339:Drug Compounding; D004435:Eating; D005215:Fasting / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D007273:Injections, Intramuscular; D007408:Intestinal Absorption; D008593:Menopause / Q000378:metabolism; D008875:Middle Aged; D011374:Progesterone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011446:Prospective Studies
D011374:Progesterone