A pharmacokinetic and tolerability evaluation of two continuous subcutaneous infusion systems compared to an oral controlled-release morphine

The pharmacokinetic profiles, safety and tolerability of continuous subcuta neous infusion with a novel drug deliver system (the MEDIPAD system) was co mpared to a standard infusion pump (the CADD-Micro) and to controlled-relea se tablets (MS Contain) for the administration of morphine sulfate. This wa s a single-centre, open-label, three-treatment study conducted in 24 male a nd female healthy voluteers. The mean age was 40.6 yr (SD = +/- 12.27). A t hree treatment design was chosen to compare differences between modes of ad ministration within each subject to minimize the impact of intersubject var iability: Treatment A was a continuous 48-hr subcutaneous infusion of morph ine sulfate (165.6 mg at a rate of 3.45 mg/hr) with the MEDIPAD system atta ched to the chest, Treatment B was a series of four oral doses of morphine sulfate (120 mg each) at 12-hr intervals, and Treatment C was a continuous 48-hr subcutaneous infusion of morphine sulfate (163.2 mg at a rate of 3.40 mg/hr) with the CADD-Micro device attached to the chest. Subjects began tr eatment after eligibility was established and informed consent was obtained . The primary pharmacokinetic parameters (AUC, C-max) for the two devices w ere similar; 90% confidence intervals showed that the MEDIPAD system was bi oequivalent to the CADD-Micro in terms of both rate and extent of morphine absorption. The mean morphine plasma concentration versus time plot suggest ed that plasma concentrations rise more rapidly with the MEDIPAD device tha n with the CADD-Micro or oral administrations. The MEDIPAD system showed mi ld application and injection site reactions; there were no site reactions f or the CADD-Micro or oral doses. As expected nausea, somnolence, and abdomi nal pain occured more frequently in the oral treatment than the two infusio n devices. These data suggest that the MEDIPAD system, which is currently u ndergoing clinical evaluation, is an acceptable alternative to the traditio nal oral treatment of morphine sufate for delivery of analgesics as it allo ws rapid absorption of morphine; is small, easy to use, and disposable; and achieves plasma levels that are essentially equal to other standard infusi on pumps. (C) U.S Cancer Pain Relief Committee, 2000.