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 subcutaneous infusion with a novel drug deliver system (the MEDIPAD system) was compared to a standard infusion pump (the CADD-Micro) and to controlled-release tablets (MS Contin) for the administration of morphine sulfate. This was a single-center, open-label, three-treatment study conducted in 24 male and female healthy volunteers. The mean age was 40.6 yr (SD = +/- 12.27). A three treatment design was chosen to compare differences between modes of administration within each subject to minimize the impact of intersubject variability: Treatment A was a continuous 48-hr subcutaneous infusion of morphine sulfate (165.6 mg at a rate of 3. 45 mg/hr) with the MEDIPAD system attached 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 treatment after eligibility was established and informed consent was obtained. The primary pharmacokinetic parameters (AUC, C(max)) for the two devices were similar; 90% confidence intervals showed that the MEDIPAD system was bioequivalent to the CADD-Micro in terms of both rate and extent of morphine absorption. The mean morphine plasma concentration versus time plot suggested that plasma concentrations rise more rapidly with the MEDIPAD device than with the CADD-Micro or oral administrations. The MEDIPAD system showed mild application and injection site reactions; there were no site reactions for the CADD-Micro or oral doses. As expected nausea, somnolence, and abdominal pain occurred more frequently in the oral treatment than the two infusion devices. These data suggest that the MEDIPAD system, which is currently undergoing clinical evaluation, is an acceptable alternative to the traditional oral treatment of morphine sulfate for delivery of analgesics as it allows rapid absorption of morphine; is small, easy to use, and disposable; and achieves plasma levels that are essentially equal to other standard infusion pumps.
Mikkelsen Lynch
P
P
Elan Pharmaceutical Research Corporation, Gainesville, GA 30504, USA.
Butler
J
J
Huerta
D
D
Tsals
I
I
Davidson
D
D
Hamm
S
S
D000284:Administration, Oral; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004867:Equipment Design; D005260:Female; D006801:Humans; D007260:Infusion Pumps; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*
D000701:Analgesics, Opioid; D009020:Morphine