Postoperative analgesia with fentanyl: pharmacokinetics and pharmacodynamics of constant-rate i.v. and transdermal delivery.

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 double-blinded fashion either placebo (n = 6) or fentanyl (n = 39) i.v. at one of four dose rates (25, 50, 100 or 125 micrograms 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-micrograms 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 micrograms h-1 and three of nine patients receiving 125 micrograms 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. Post-operative morphine requirements were minimal (less than 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.