Pharmacokinetics of piritramide after an intravenous bolus in surgical patients.
BACKGROUND
Piritramide is a synthetic opioid analgesic which is commonly used for postoperative analgesia. It is structurally related to meperidine, exhibiting full mu-receptor agonism. Pharmacokinetic data of the drug have not been reported so far.


METHODS
Plasma protein binding of piritramide was studied in vitro. The kinetics were examined after a single intravenous bolus (0.2 mg/kg) in 10 male patients aged 22-53 years undergoing elective minor surgery. Plasma and urine concentrations were determined by gas chromatography in samples drawn before and after the bolus. The concentration vs. time data were evaluated by nonlinear regression analysis, and the mean values and SD of the individual pharmacokinetic parameters were calculated. A three-compartment body 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 piritramide 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 physiological range.


CONCLUSIONS
Since the elimination half-life of piritramide 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 accumulation that may lead to adverse effects.
Department of Anaesthesiology, University of Göttingen, FRG.
D
D
Kietzmann
I
I
Briede
T
T
Bouillon
U
U
Gundert-Remy
D
D
Kettler
D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001798:Blood Proteins / Q000378:metabolism; D002849:Chromatography, Gas; D003404:Creatinine / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D013511:Minor Surgical Procedures; D010892:Pirinitramide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011485:Protein Binding
D000701:Analgesics, Opioid; D001798:Blood Proteins; D010892:Pirinitramide; D003404:Creatinine