POSTOPERATIVE ANALGESIA WITH FENTANYL: PHARMACOKINETICS AND PHARMACODYNAMICS OF CONSTANT-RATE I.V. AND TRANSDERMAL DELIVERY †

Abstract

We have investigated the use of constant-rate delivery of fentanyl by i.v. and transdermal routes for the treatment of pain after major surgery. Forty-five males, ASA I–III, received in a doubleblinded fashion either placebo (n = 6) or fentanyl (n = 39) i.v. at one of four dose rates (25, 50, 100 or 125 μg h⁻¹). Stable serum concentrations of fentanyl were produced by the end of surgery and were maintained for a total of 24 h. Calculated clearance of fentanyl was 1.05±0.38 litre min⁻¹ and was not related to weight or age. Both the 100- and 125-μg h⁻¹ dose rates produced significant analgesic efficacy as assessed by postoperative morphine requirements. Mean serum concentrations of fentanyl in these groups were 1.42±0.14 (SD) and 1.90±0.30 ng ml⁻¹, respectively. One of 10 patients receiving fentanyl 100 μg h⁻¹ and three of nine patients receiving 125 μg h⁻¹ had evidence of respiratory depression. Eight additional patients were treated with a transdermal drug delivery system containing fentanyl (TTS-fentanyl). Steady-state serum concentrations in this group were 2.15±0.92 (SD) ng ml⁻¹. Postoperative morphine requirements were minimal (< 0.5 mg h⁻¹) and PaCO₂ remained acceptable in all patients. Serum concentrations of fentanyl increased slowly (15 h to plateau) and decreased slowly (apparent half-life, 21 h). We conclude that delivery of analgesic doses of fentanyl is feasible by the transdermal route.