THE CSF AND PLASMA PHARMACOKINETICS OF SUFENTANIL AFTER INTRATHECAL ADMINISTRATION

Eight patients (7 men and 1 woman, 45-68 yr old) scheduled to undergo thoracotomy were given, preoperatively, 15-mu-g sufentanil in the lumbar intrathecal space for a study of cerebrospinal fluid (CSF) and plasma kinetics of sufentanil. Multiple samples of plasma and CSF from the lumbar region were obtained through indwelling catheters for 12 h and analyzed for sufentanil by radioimmunoassay. Pharmacokinetic parameters were derived by noncompartmental analysis. In plasma, the maximal concentration of sufentanil appeared after 0.65 +/- 0.17 h (mean +/- SEM). No equilibrium was reached between the sufentanil concentration in CSF and plasma, but the CSF/plasma concentration ratio declined from approximately 140 at 2 h to about 15 at 10 h. Extrapolation indicates that another 10 h would be required before the concentration in CSF would equal that in plasma. The mean residence time (MRT) of sufentanil in CSF was 0.92 +/- 0.08 h and in plasma was 6.8 +/- 0.6 h. The volume of distribution at steady state (V(ss)) in the subarachnoid compartment was 1.54 +/- 0.39 ml/kg, and the clearance from the CSF was 27 +/- 5 mu-l.kg-1.min-1. The intrathecal administration of 15-mu-g sufentanil at the beginning of the operation did not produce analgesia that lasted into the postoperative period. Most patients has urinary retention, but none experienced any serious complications. This study demonstrates that the lipophilic opioid sufentanil undergoes rapid clearance from CSF and absorption to plasma after intrathecal administration. These pharmacokinetic characteristics are slower for the less lipophilic opioids meperidine and morphine. The rapid pharmacokinetics of sufentanil explain its rapid onset of action and short-lasting effects.