Pharmacokinetics of Lidocaine and Bupivacaine following Subarachnoid Administration in Surgical Patients

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Abstract
The pharmacokinetics of lidocaine and bupivacaine following subarachnoid administration were stdied in 12 surgical patients using a stable isotope method. After subarachnoid administration of the agent to be evaluated, a deuterium-labelled analogue analogue was administered intravenously. Blood samples were collected for 24 h. Plasma concentrations of the unlabelled and the deuterium-labelled local anesthetics were determined using a combination of capillary gas chromatography and mass fragmentography. Bi-exponential functions were fitted to the plasma concentration-time data of the deuterium-labelled local anesthetics. The progression of the absorption was evaluated using deconvolution. Mono- and bi-exponential functions were then fitted to the fraction absorbed versus time data. The distribution and elimination half-lives of the deuterium-labelled analogues were 25 .+-. 13 min (mean .+-. SD) and 121 .+-. 31 min for lidocaine and 19 .+-. 10 min and 131 .+-. 33 min for bupivacaine. The volumes of the central compartment and steady-state volumes of distribution were: lidocaine 57 .+-. 101 and 105 .+-. 25 l, bupivacaine 25 .+-. 61 and 63 .+-. 22 l. Total plasma clearance values averaged 0.97 .+-. 0.21 l/min for lidocaine and 0.56 .+-. 0.14 l/min for bupivacaine. The absorption of lidocaine could be described by a single first order absorption process, characterized by a half-life of 71 .+-. 17 min in five and six patients. The absorption of bupivacaine could be described adequately assuming two parallel first order absorption processes in all six patients. The half-lives, characterizing the fast and slow absorption processes of bupivacaine, were 50 .+-. 27 min and 408 .+-. 275 min, respectively. The fractions of the dose, absorbed in the fast and slow processes, were 0.35 .+-. 0.17 and 0.61 .+-. 0.06, respectively. The results indicate that both local anesthetics are completely absorbed intact from the subarachnoid space into the general circulation.