Pharmacokinetics of Pethidine During Anaesthesia and Patient‐Controlled Analgesic Therapy

Abstract

The pharmacokinetics of pethidine has been studied in 12 patients subjected to major intraabdominal surgery. Pethidine and norpethidine were analyzed in plasma samples collected during anesthesia and during patientcontrolled administration of small intravenous doses of pethidine in the early postoperative period. A second study on the pharmacokinetics of pethidine was performed on the 3-5th postoperative day. The plasma clearance of pethidine was significantly lower in the peroperative study (8.9f 1.8 ml kg. min-l) compared with the postoperative study (12.0k3.1 ml.kg.min"). Volume of distribution (Vd) was not significantly influenced, being 4.25k 1.72 1.kg-l peroperatively and 3.14f0.84 1.kg-I postoperatively. Elimination half-life decreased from 5.91 k3.57 h peroperatively to 3.25f 1.40 h postoperatively. The kineticsofpethidine in the postoperative study agreed with pethidine kinetics reported for healthy volunteers. The fraction of unbound pethidine decreased from 0.26f0.1 peroperatively to 0.18 f 0.1 postoperatively. Norpethidine, a metabolite ofpethidine,has been claimed to be responsible for several side effects like respiratory depression and convulsions during pethidine therapy. No side effect attributable to norpethidine was observed in the self-administration period. Norpethidine plasma concentrations did not exceed 500 ng/ml. The altered pethidine pharmacokinetics during anesthesia and the ensuing postoperative hours and the interindividual differences of the disposition of the drug strongly suggest that pethidine should be given by individualized regimens in surgical patients.

Pharmacokinetics and ventilatory effects of intravenous oxycodone in postoperative children [see comments]

“…Halothane anaesthesia decreases the metabolic clearance of drugs in liver [16]. Thus, the differences in oxycodone metabolism between children and adults may be even greater.…”

“…First, assuming no equilibration delay between drug in plasma and that at the site of action (C=Ce). Secondly, by accounting for the possibility of a delay between the time-curves of plasma oxycodone concentration and effect using a pharmacokinetic-pharmacodynamic link model [16]. There was no provision for a possible equilibration delay between end-tidal concentration of halothane and its concentration at the effect site.…”