Morphine Bioavailability from a Topical Gel Formulation in Volunteers

Although available therapies provide relief to many patients with cancer-related pain, swallowing difficulties or intestinal obstruction may preclude oral analgesic delivery in some. Topical morphine might provide an alternate delivery form but morphine bioavailability from a topical gel formulation has not been reported in humans. We conducted a randomized, placebo-controlled, double-blind, crossover study of five volunteers after they provided institutionally-approved, written, informed consent. They were admitted to the Northwestern University General Clinical Research Center twice, being randomly assigned to receive either 1 mL of morphine compounded at 10 mg/mL in pluronic lecithin organogel (PLO) base applied to the wrist and 1 mL of normal saline administered subcutaneously, or 1 mL of topical drug-free PLO base and 1 mL of subcutaneous morphine, 3 mg/mL, the first time and the opposite combination the second. Seventeen blood samples were collected from 5 minutes to 10 hours after dose administration for morphine concentration determination. Plasma samples were prepared by solid-phase extraction and morphine concentrations measured by a mass spectrometric technique with a linear range of 0.5–500 ng/mL. Bioavailability of the topical formulation relative to the subcutaneous dose was to be estimated from doses and the plasma morphine concentration versus time relationships. Because morphine was seldom detected in plasma samples after topical administration and was unquantifiable when it was, the low bioavailability of topical morphine was unquantifiable. These results suggest that topical administration of morphine compounded in a PLO base for transdermal drug delivery is unlikely to provide relief of cancer-related pain.