Population pharmacokinetics of piritramide in surgical patients

Background: Piritramide is a synthetic opioid used for postoperative analge sia in several European countries. The authors present a mixed-effects mode l of its population pharmacokinetics In patients undergoing surgery. Methods: After institutional approval and informed patient consent was obta ined, 29 patients who were classified as American Society of Anesthesiologi sts physical status I or II and aged 21-82 yr were enrolled in the study. T hey received 0.2 mg/kg piritramide as an intravenous bolus before anesthesi a was induced. Central venous blood samples were drawn for as long as 48 h after administration of the drug. The plasma concentration of piritramide w as determined by gas chromatography, The concentration-time data were analy zed by mixed-effects modeling. Target-controlled infusions and intermittent bolus regimens were simulated to identify a regimen suitable for patient-c ontrolled analgesia based on population pharmacokinetics and published phar macodynamic data. Results: The pharmacokinetics of piritramide were described adequately by a linear three-compartment model. Patient age and weight were significant co variates. The values of the pharmacokinetic parameters are: V-1 = 50.5 [1], V-2 = 150 . (1 + 9.32 . 10(-3). (age - 47 yr)) [1], V-3 = 212 . (1 + 6.37 10-3 (age - 47 yr)) [1], Cl-1 = 0.56 . (1 - 6.14 10(-3) (age - 47 yr)) [1/m in], Cl-2 = 8.25 . (1 + 2.02 . 10(-2) . (Wt - 74 kg)) [1/min], Cl-3 = 0.80 [1/min]. The age of 47 yr and the weight of 74 kg refer to the median value s for these factors in the patients studied. Rapid distribution, slow distr ibution, and elimination half-lives for the median patient are 0.05, 1.34, and 10.43 h, respectively. The context-sensitive half-time after a 24-h inf usion is predicted at 10.5 h in a 75-yr-old patient compared with 7 h for t he median patient. Conclusions: Piritramide is distributed extensively and eliminated slowly.. The pharmacokinetic profile of the drug allows for intermittent bolus admi nistration even when constant effect compartment concentrations are desirab le, e.g., for PLA.