Pharmacodynamic modelling of the analgesic effects of piritramide in postoperative patients.
BACKGROUND
The concentration-effect relationship of piritramide, a synthetic opioid analgesic predominantly used for postoperative analgesia and analgosedation, has not been reported so far.


METHODS
Twenty-four patients of both genders aged 58.1 (11.7) yr (mean (SD)) received inhalational anaesthesia for abdominal surgery. Postoperative pain was assessed with a visual analogue scale (VAS). Analgesia was provided with piritramide, infused at a rate of 7 micrograms.kg-1.min-1 until analgesia was considered sufficient (VAS < 25) or up to a maximum dose of 0.2 mg/kg. The plasma concentrations of piritramide were determined by gas chromatography. An inhibitory fractional sigmoid Emax-model was used to describe the relation between effect site concentration and perceived pain.


RESULTS
The equilibration half-life between plasma and effect site concentrations (T1/2 (keo)) was 16.8 min (median; range: 4.4-41.6 min). The steady-state plasma concentration required to produce 50% of maximum analgesia (EC50) was 12.1 ng/ml (range: 2.9-29.8 ng/ml) and correlated with initial pain intensity. The slope factor gamma was 1.9 (range: 0.5-6.1) and increased with age. Clinically relevant respiratory depression did not occur. Due to the relatively large equilibration half-life of the effect compartment, the context-sensitive half-time of the effect site concentrations after short-time administration (< 2 h) clearly exceeded those of alfentanil, sufentanil, and fentanyl.


CONCLUSIONS
The analgesic effect of piritramide was adequately described by an inhibitory fractional Emax-model. In order to overcome the pronounced hysteresis, piritramide should initially be administered as an intravenous bolus of at least 5 mg.
Kietzmann
D
D
Department of Anaesthesiology, University of Göttingen, FRG.
Bouillon
T
T
Hamm
C
C
Schwabe
K
K
Schenk
H
H
Gundert-Remy
U
U
Kettler
D
D
D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010149:Postoperative Pain / Q000188:drug therapy*; D010892:Pirinitramide / Q000493:pharmacokinetics / Q000494:pharmacology*
D000701:Analgesics, Opioid; D010892:Pirinitramide