BIOAVAILABILITY OF INTRANASAL PROMETHAZINE DOSAGE FORMS IN DOGS

Intramuscular promethazine (PMZ) is used aboard the US Space Shuttle t o ameliorate symptoms of space motion sickness. Bioavailability after an oral dose of PMZ during space flight is thought to be impaired beca use of gastrointestinal disturbances associated with weightlessness an d space motion sickness. In an attempt to find an alternative dosage f orm 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 admin istered as two intranasal dosage forms and as an intramuscular (i.m.) dose to three dogs in a randomised cross-over design. Serial blood sam ples 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. dos age form was more rapid and complete than from the myverol cubic gel f ormulation or from an i.m. injection. Bioavailability of the microsphe re 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 pr omise as an effective non-invasive alternative for treating space moti on sickness due to its rapid absorption and bioavailability equivalent to the i.m. dose. (C) 1998 The Italian Pharmacological Society.