Patient-controlled analgesic therapy. Part I: Pharmacokinetics of pethidine in the per- and postoperative periods

The influence of anaesthesia and surgery on the pharmacokinetics of pethidine (meperidine) was studied in 12 patients. Plasma pethidine concentrations in central venous blood collected during anaesthesia and the ensuing postoperative hours were by gas chromatography with electron capture detection. Postoperative analgesia was accomplished by patient-controlled intravenous administration of small doses of pethidine. The NONLIN program was used to calculate pharmacokinetic parameters for each individual. A single dose study of pethidine kinetics was carried out in all patients 3 to 5 days postoperatively. Mean +/- SD for peroperative Vd area was 4.3 +/- 1.7L/kg and for the elimination half-life was 6.1 +/- 3.6h. In the postoperative period Vdarea was 3.2 +/- 0.8L/kg and the elimination half-life was 3.2 +/- 1.4h. Plasma clearance increased from a peroperative value of 8.9 +/- 1.9 ml/min/kg to a postoperative value of 12 +/- 3.0 ml/min/kg. The changes in elimination half-life and plasma clearance are significant. The postoperative pharmacokinetics of pethidine were in accordance with those reported for healthy volunteers. The fraction of unbound pethidine was significantly reduced postoperatively - from 0.26 +/- 0.10 (peroperatively) to 0.18 +/- 0.10 (3 to 5 days later).