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Piritramide and Alfentanil display similar respiratory depressant potency
Author(s) -
Bouillon T.,
Garstka G.,
Stafforst D.,
Shafer S.,
Schwilden H.,
Hoeft A.
Publication year - 2003
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 - 10.1046/j.1399-6576.2003.00251.x
Subject(s) - alfentanil , medicine , potency , anesthesia , nonmem , pharmacodynamics , depressant , respiratory system , pharmacokinetics , pharmacology , fentanyl , chemistry , biochemistry , in vitro
Background: The question whether some opioids exert less respiratory depression than others has not been answered conclusively. We applied pharmacokinetic/pharmacodynamic (PKPD) modeling to obtain an estimate of the C 50 for the depression of CO 2 elimination as a measure of the respiratory depressant potency of alfentanil and piritramide, two opioids with vastly different pharmacokinetics and apparent respiratory depressant action. Methods: Twenty‐three patients received either alfentanil (2.3 µg·kg −1 ·min −1 , 14 patients, as published previously) or piritramide (17.9 µg·kg −1 ·min −1 , nine patients) until significant respiratory depression occurred. Opioid pharmacokinetics and the arterial PCO 2 (PaCO 2 ) were determined from frequent arterial blood samples. An indirect response model accounting for the respiratory stimulation due to increasing PaCO 2 was used to describe the PaCO 2 data. Results: The following pharmacodynamic parameters were estimated with NONMEM [population means and interindividual variability (CV)]: k elCO2 (elimination rate constant of CO 2 ) 0.144 (–) min −1 , F (gain of the CO 2 response) 4.0 (fixed according to literature values) (28%), C 50 (both drugs) 61.3 µg l −1 (41%), k eo alfentanil 0.654 (–) min −1 and k eo piritramide 0.023 (–) min −1 . Assigning separate C 50 values for alfentanil and piritramide did not improve the fit compared with a model with the same C 50 . Conclusion: Since the C 50 values did not differ, both drugs are equally potent respiratory depressants. The apparently lower respiratory depressant effect of piritramide when compared with alfentanil is caused by slower equilibration between the plasma and the effect site. Generalizing our results and based on simulations we conclude that slowly equilibrating opioids like piritramide are intrinsically safer with regard to respiratory depression than rapidly equilibrating opioids like alfentanil.