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 7 days between dosages. SETTING: Academic institution. PARTICIPANTS: Fifteen normal postmenopausal women. INTERVENTIONS: 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. 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.

Potential for nonnarcotic analgesics to save personnel costs associated with controlling injectable morphine and meperidine.

The personnel costs associated with handling injectable morphine and meperidine in five hospitals were determined, and the potential savings from using a non-controlled analgesic as an alternative were estimated. Five distinctly different U.S. hospitals were selected for study. Tasks involved in the acquisition, distribution, and preparation of injectable doses of morphine and meperidine were identified, and data on the personnel time required to complete each task were collected. Personnel costs were calculated on the basis of per minute wage rates, and costs that could be avoided if injectable morphine and meperidine were replaced by a nonnarcotic analgesic were estimated by determining the relevance of each task to the use of a noncontrolled injectable agent. The total personnel cost of controlling morphine and meperidine ranged from $0.55 to $0.93 per dose; the weighted average cost was $0.64 per dose. The savings that could be realized by replacing injectable morphine and meperidine with a noncontrolled injectable analgesic ranged from $0.13 to $0.36 per dose; the weighted average avoidable cost was $0.23 per dose. Eliminating the need to control these medications might not result in savings in dollar terms but would free health-care workers to perform other tasks. If costs are interpreted in terms of lost opportunities, such savings are real. The use of a nonnarcotic injectable analgesic in place of injectable morphine and meperidine could save approximately $0.23 in personnel costs per dose at the study hospitals.