Cerebrospinal fluid bioavailability and pharmacokinetics of bupivacaine and lidocaine after intrathecal and epidural administrations in rabbits usingmicrodialysis

The aim of this work was to study the cerebrospinal fluid (CSF) bioavailabi lity and pharmacokinetics of bupivacaine (BUP) and lidocaine (LID) administ ered separately in rabbits using microdialysis with retrodialysis calibrati on. Microdialysis probe and catheters were inserted under control of the vi ew in the intrathecal or epidural spaces. The epidural disposition of BUP a nd LID after epidural administration of low (0.69 mu M) and high (6.9 mu M) doses was studied. Then, the intrathecal and plasma dispositions after sep arate intrathecal (0.2 mu M) and epidural administration (6.9 mu M) were in vestigated. The CSF binding of BUP and LID was linear in a range from 50 to 500 mu g/ml, and the mean unbound CSF fraction at a concentration of 100 m u g/ml was 39.3 +/- 2.3% for BUP and 75.8 +/- 7.7% for LID Epidural and int rathecal disposition of BUP and LID showed a biexponential decline. After e pidural administration, the CSF concentrations of BUP and LID were much hig her than those in plasma. After intrathecal administration, the plasma conc entrations were below the limit of quantitation. Although the absorption ra te of BUP appeared higher than that of LID, the mean CSF bioavailability of epidural BUP and LID was 5.5 and 17.7%, respectively. The unexpectedly hig her CSF bioavailability of LID, the less lipophilic drug, may result from t he difference in the processes competing for drug epidural removal.