Sevoflurane Remifentanil Interaction
Adult
Male
Methyl Ethers
PHARMACOKINETICS
INCISION
PROPOFOL
Models, Biological
Remifentanil
Sevoflurane
Young Adult
03 medical and health sciences
0302 clinical medicine
Piperidines
Humans
Drug Interactions
Prospective Studies
ALVEOLAR CONCENTRATION
FENTANYL
Drug Synergism
ISOFLURANE
PHARMACODYNAMICS
MIDAZOLAM
3. Good health
REDUCTION
Anesthetics, Inhalation
Female
REQUIREMENTS
Anesthetics, Intravenous
DOI:
10.1097/aln.0b013e318242a2ec
Publication Date:
2012-01-06T14:28:05Z
AUTHORS (8)
ABSTRACT
Background
Various pharmacodynamic response surface models have been developed to quantitatively describe the relationship between two or more drug concentrations with their combined clinical effect. We examined the interaction of remifentanil and sevoflurane on the probability of tolerance to shake and shout, tetanic stimulation, laryngeal mask airway insertion, and laryngoscopy in patients to compare the performance of five different response surface models.
Methods
Forty patients preoperatively received different combined concentrations of remifentanil (0-12 ng/ml) and sevoflurane (0.5-3.5 vol.%) according to a criss-cross design (160 concentration pairs, four per patient). After having reached pseudosteady state, the response to shake and shout, tetanic stimulation, laryngeal mask airway insertion, and laryngoscopy was recorded. For the analysis of the probability of tolerance, five different interaction models were tested: Greco, Reduced Greco, Minto, Scaled C50(O) Hierarchical, and Fixed C50(O) Hierarchical model. All calculations were performed with NONMEM VI (Icon Development Solutions, Ellicott City, MD).
Results
The pharmacodynamic interaction between sevoflurane and remifentanil was strongly synergistic for both the hypnotic and the analgesic components of anesthesia. The Greco model did not result in plausible parameter estimates. The Fixed C50(O) Hierarchical model performed slightly better than the Scaled C50(O) Hierarchical and Reduced Greco models, whereas the Minto model fitted less well.
Conclusion
We showed the importance of exploring various surface model approaches when studying drug interactions. The Fixed C50(O) Hierarchical model fits our data on sevoflurane remifentanil interaction best and appears to be an appropriate model for use in hypnotic-opioid drug interaction.
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