Intramuscular
promethazine (PMZ) is used aboard the US Space Shuttle to ameliorate symptoms of
space motion sickness. Bioavailability after an oral dose of PMZ during space flight is thought to be impaired because of gastrointestinal disturbances associated with weightlessness and
space motion sickness. In an attempt to find an alternative
dosage form for use in space, we evaluated two intranasal (i.n.)
dosage forms of PMZ in dogs for absorption and bioavailability relative to that of an equivalent intramuscular dose.
Promethazine (5 mg kg-1) was administered as two intranasal
dosage forms and as an intramuscular (i.m.) dose to three dogs in a randomised cross-over design. Serial blood samples were taken and analysed for PMZ concentrations and the absorption and bioavailability of PMZ were calculated for the three
dosage forms. PMZ absorption from the
carboxymethyl cellulose microsphere i.n.
dosage form was more rapid and complete than from the myverol cubic gel formulation or from an i.m. injection. Bioavailability of the
microsphere formulation was also greater than that of the gel formulation (AUC 3009 vs 1727 ng h ml-1). The bioavailability of the two i.n.
dosage forms (relative to that of the i.m. injection) were 94% (
microsphere) and 54% (gel). The i.n.
microsphere formulation of PMZ offers great promise as an effective non-invasive alternative for treating
space motion sickness due to its rapid absorption and bioavailability equivalent to the i.m. dose.