PHARMACOKINETICS OF PIRITRAMIDE AFTER AN INTRAVENOUS BOLUS IN SURGICAL PATIENTS

Background: Piritramide is a synthetic opioid analgesic which is commo nly used for postoperative analgesia. It is structurally related to me peridine, exhibiting full mu-receptor agonism. Pharmacokinetic data of the drug have not been reported so far. Methods: Plasma protein bindi ng of piritramide was studied in vitro. The kinetics were examined aft er a single intravenous bolus (0.2 mg/kg) in 10 male patients aged 22- 53 years undergoing elective minor surgery. Plasma and urine concentra tions were determined by gas chromatography in samples drawn before an d after the bolus. The concentration vs. time data were evaluated by n onlinear regression analysis, and the mean values and SD of the indivi dual pharmacokinetic parameters were calculated. A three-compartment b ody model was fitted to the data. Results: The volume of distribution at steady state was 4.7 (0.7) l/kg, systemic plasma clearance was 7.8 (1.5) (mean (SD)) ml/kg/min. Renal clearance of unchanged piritramide was negligible (0.13 (0.09) ml/kg/min). The terminal elimination half- life was 8.0 (1.4) h. In vitro, the free fraction in plasma of piritra mide did not change over the therapeutic concentration range (5.5 (1.3 )% at a pH of 7.35) but decreased considerably with pH within the phys iological range. Conclusion: Since the elimination half-life of piritr amide appears to exceed the duration of clinically effective analgesia observed during the treatment of acute pain, the dose of piritramide should be titrated carefully during long-term treatment to avoid accum ulation that may lead to adverse effects.