Relationship between the pharmacokinetics and the analgesic and respiratory pharmacodynamics of epidural sufentanil

Gideon Koren, Alan N. Sandier, Julia Klein, Wilma C. Whiting, Larry C. Lau, Paul Slavchenko, Denise Daley

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20 Scopus citations


To establish the relationships between epidural sufentanil analgesia and respiratory effects and to determine the pharmacoldnetics of the drug, 22 adult patients undergoing thoracotomy were put into a randomized, double-blind study and received either 30, 50, or 75 μg per dose in 20 ml normal saline solution. Repeated doses were given on request for the 24-hour study period. There was a weak but significant nonlinear correlation between length of effective analgesia and the cumulative dose of the drug (r = 0.26, π < 0.001). In 12 of 22 patients, the maximal length of effective analgesia was reached before the last dose and the effect tended to taper off thereafter. The mean maximal length of effective analgesia was 4.69 ± 0.32 hours (mean ± SEM), whereas the length of effective analgesia with the last dose was only 3.34 ± 0.46 hours (p < 0.0005). There was a significant correlation between the peak serum concentrations of sufentanil during the dose interval and the length of effective analgesia (r = 0.44, p < 0.0001). Area under the concentration-time curve was proportional to the size of the epidural dose, and with all three doses tested there was a gradual accumulation of sufentand in the serum. Mean time-to-peak concentration (tmax) increased with repeated doses (p < 0.05). Mean serum concentration of sufentanil during periods of slow respiratory rate (0.47 ± 0.05 ng/ml) was significantly higher than during episodes without adverse respiratory effects (0.37 ± 0.05 ng/ml, p < 0.05). The above data suggest that an important part of the analgesic and adverse effects of sufentanil are mediated centrally, after this opioid is absorbed systemically.

Original languageEnglish
Pages (from-to)458-462
Number of pages5
JournalClinical Pharmacology and Therapeutics
Issue number4
StatePublished - Oct 1989
Externally publishedYes


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