The Cerebrospinal Fluid and Plasma Pharmacokinetics of Sufentanil After Thoracic or Lumbar Epidural Administration

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Abstract
The cerebrospinal fluid (CSF) and plasma pharmacokinetics of sufentanil were studied in 29 adult patients undergoing thoracotomy under general anesthesia. Sufentanil, 75 micrograms, diluted in 10 mL saline, was given preoperatively in either the lumbar or thoracic epidural space to 14 and 15 patients, respectively. Lumbar CSF and plasma were frequently sampled for 10 h and analyzed for sufentanil concentration by radioimmunoassay. In plasma, the area under the concentration curve (AUC) did not differ between the groups. The fraction of the lumbar epidural dose found in CSF was calculated to be 2.7%. The time to peak CSF sufentanil concentration differed (P < 0.01) after epidural administration in the lumbar (0.76 +/- 0.50 h) and thoracic (2.1 +/- 1.4 h) region. In the lumbar group, the AUC and Cmax values in CSF were 19 (P < 0.01) and 45 (P < 0.01) times higher than in plasma, and 4.7 (P < 0.01) and 8.2 (P < 0.001) times higher than in CSF in the thoracic group. The decline in sufentanil concentration was more rapid in CSF than plasma; in the lumbar group the CSF/plasma concentration-ratio was eight and five at 6 and 10 h, respectively, after sufentanil administration. This study shows that after epidural administration sufentanil concentrations are higher in CSF than in plasma, and are highly localized within CSF to the site of administration.