CONTEXT: Transdermal absorption of morphine into the systemic circulation through intact skin has not been reported. OBJECTIVES: To describe a novel transdermal formulation for a morphine hydrochloride patch consisting of polyethylene sponge foam as the retaining agent and adjusted proportions of morphine hydrochloride and adjunctive drugs. METHODS: In this study, the transdermal morphine hydrochloride patch was administered to intact skin in five subjects and the plasma concentrations of morphine and its metabolites were examined. RESULTS: Morphine was absorbed systemically, producing plasma morphine concentrations above the assay detection limit by at least 24 hours after attachment of patches containing a total dose of 180mg of morphine. The levels gradually increased in a time-dependent manner without serious events. The area under the concentration-time curve from 0 to 72 hours (AUC(0-72)) values for morphine, morphine-6-glucuronide, and morphine-3-glucuronide were 60.4±13.4, 133.7±17.4, and 861.5±126.7ng·h/mL, respectively. The mean plasma area under the concentration-time curve from 0 to 72 hours ratio for morphine-6-glucuronide relative to morphine was 2.64. CONCLUSION: These data provide useful information for developing a transdermal morphine system.
CONTEXT: Transdermal absorption of morphine into the systemic circulation through intact skin has not been reported. OBJECTIVES: To describe a novel transdermal formulation for a morphine hydrochloride patch consisting of polyethylene sponge foam as the retaining agent and adjusted proportions of morphine hydrochloride and adjunctive drugs. METHODS: In this study, the transdermal morphine hydrochloride patch was administered to intact skin in five subjects and the plasma concentrations of morphine and its metabolites were examined. RESULTS:Morphine was absorbed systemically, producing plasma morphine concentrations above the assay detection limit by at least 24 hours after attachment of patches containing a total dose of 180mg of morphine. The levels gradually increased in a time-dependent manner without serious events. The area under the concentration-time curve from 0 to 72 hours (AUC(0-72)) values for morphine, morphine-6-glucuronide, and morphine-3-glucuronide were 60.4±13.4, 133.7±17.4, and 861.5±126.7ng·h/mL, respectively. The mean plasma area under the concentration-time curve from 0 to 72 hours ratio for morphine-6-glucuronide relative to morphine was 2.64. CONCLUSION: These data provide useful information for developing a transdermal morphine system.