Pharmacokinetics of lidocaine and bupivacaine and stable isotope labelled analogues: a study in healthy volunteers.

Abstract

The pharmacokinetics of lidocaine and bupivacaine and tri-deuteromethyl-labelled lidocaine and bupivacaine were investigated in healthy volunteers. The deuterium-labelled and the unlabelled form of the drug to be investigated were simultaneously infused in 10 min. Plasma concentrations were determined using a combination of capillary gas chromatography and mass fragmentography. Bi-exponential functions were fitted to the plasma concentration-time data. The mean distribution and elimination half-lives were 8.4 +/- 5.9 min and 96 +/- 26 min for lidocaine, 9.2 +/- 7.0 min and 98 +/- 27 min for deuterium-labelled lidocaine, 15.3 +/- 9.9 min and 111 +/- 32 min for bupivacaine, and 15.2 +/- 10.9 min and 109 +/- 31 min for deuterium-labelled bupivacaine, respectively. The mean volumes of the central compartment and mean steady state volumes of distribution were: lidocaine 37 +/- 151 and 97 +/- 201, deuterium-labelled lidocaine 39 +/- 161 and 98 +/- 181, bupivacaine 27 +/- 111 and 66 +/- 231 and deuterium-labelled bupivacaine 28 +/- 121, and 65 +/- 221, respectively. The respective mean plasma clearances were 0.88 +/- 0.181 min-1, 0.87 +/- 0.181 min-1, 0.61 +/- 0.151 min-1, and 0.62 +/- 0.171 min-1. The results of the study indicate that substitution of a deuterated methyl group does not alter the pharmacokinetics of lidocaine and bupivacaine in healthy subjects.