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Influence of Simulated Weightlessness on the Intramuscular and Oral Pharmacokinetics of Promethazine in 12 Human Volunteers
Author(s) -
Gandia Peggy,
Saivin Sylvie,
LeTraon Anne Pavy,
Guell Antonio,
Houin Georges
Publication year - 2006
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006291032
Subject(s) - promethazine , pharmacokinetics , medicine , bioequivalence , ambulatory , intramuscular injection , oral administration , anesthesia , area under the curve , pharmacology , route of administration , surgery
The National Aeronautics and Space Administration (NASA) recommends using promethazine to prevent and treat space motion sickness, but pharmacologic responses in space and on Earth are different. Twelve volunteers were given 50 mg promethazine orally or intramuscularly before and after 48 hours of bed rest to simulate weightlessness. The maximum measured plasma concentration (C max ), time to C max (t max ), and area under plasma concentration versus time curve from 0 to infinity (AUC inf ) were determined, and the bioequivalence was tested between bed‐rest and ambulatory status for the intramuscular and oral routes as well as between both routes for bed‐rest and ambulatory position. Simulated weightlessness did not influence the ratio AUC bed rest /AUC ambulatory after intramuscular injection, whereas a significant increase (26%) in the ratio was seen after oral administration, probably because of a prolonged contact time between promethazine and the intestinal wall associated with an increase in the intestinal transit time. The AUC was 3‐fold higher when the drug was administered by the intramuscular route during both positions. Thus, intramuscular administration could be a good alternative to the oral route.