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Pharmacodynamic modelling of the analgesic effects of piritramide in postoperative patients
Author(s) -
KIETZMANN D.,
BOUILLON T.,
HAMM C.,
SCHWABE K.,
SCHENK H.,
GUNDERTREMY U.,
KETTLER D.
Publication year - 1997
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/j.1399-6576.1997.tb04805.x
Subject(s) - medicine , sufentanil , anesthesia , alfentanil , analgesic , visual analogue scale , fentanyl , pharmacodynamics , context (archaeology) , pharmacokinetics , pharmacology , paleontology , biology
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 μg 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 E max ‐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 (T 1/2 (k eo ) was 16.8 min (median; range: 4.4–41.6 min). The steady‐state plasma concentration required to produce 50% of maximum analgesia (EC 50 ) was 12.1 ng/ml (range: 2.9–29.8 ng/ml) and correlated with initial pain intensity. The slope factor γ 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 E max ‐model. In order to overcome the pronounced hysteresis, piritramide should initially be administered as an intravenous bolus of at least 5 mg.