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

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Abstract
To establish the relationships between epidural sufentanil analgesia and respiratory effects and to determine the pharmacokinetics 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, p < 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 sufentanil 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. Clinical Pharmacology and Therapeutics (1989) 46, 458–462; doi:10.1038/clpt.1989.165