Population pharmacokinetics of piritramide in surgical patients

BACKGROUND: Piritramide is a synthetic opioid used for postoperative analgesia in several European countries. The authors present a mixed-effects model of its population pharmacokinetics in patients undergoing surgery. METHODS: After institutional approval and informed patient consent was obtained, 29 patients who were classified as American Society of Anesthesiologists physical status I or II and aged 21-82 yr were enrolled in the study. They received 0.2 mg/kg piritramide as an intravenous bolus before anesthesia was induced. Central venous blood samples were drawn for as long as 48 h after administration of the drug. The plasma concentration of piritramide was determined by gas chromatography. The concentration-time data were analyzed by mixed-effects modeling. Target-controlled infusions and intermittent bolus regimens were simulated to identify a regimen suitable for patient-controlled analgesia based on population pharmacokinetics and published pharmacodynamic data. RESULTS: The pharmacokinetics of piritramide were described adequately by a linear three-compartment model. Patient age and weight were significant covariates. The values of the pharmacokinetic parameters are: V1 = 50.5 [1], V2 = 150 x (1 + 9.32 x 10(-3) x (age - 47 yr)) [l], V3 = 212 x (1 + 6.37 x 10(-3) x (age - 47 yr)) [l], Cl1 = 0.56 x (1 - 6.14 x 10(-3) x (age - 47 yr)) [l/min], Cl2 = 8.25 x (1 + 2.02 x 10(-2) x (Wt - 74 kg)) [l/min], Cl3 = 0.80 [l/min]. The age of 47 yr and the weight of 74 kg refer to the median values for these factors in the patients studied. Rapid distribution, slow distribution, 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 infusion is predicted at 10.5 h in a 75-yr-old patient compared with 7 h for the median patient. CONCLUSIONS: Piritramide is distributed extensively and eliminated slowly. The pharmacokinetic profile of the drug allows for intermittent bolus administration even when constant effect compartment concentrations are desirable, e.g., for PLA.status: publishe