Kinetics of uptake and washout of lidocaine in rat sciatic nerve in vitro

The potency and efficacy of local anesthetics injected clinically for peripheral nerve block depends strongly on the rate of neural drug uptake. However, because diffusion into surrounding tissues and removal by the vascular system are major factors in the overall distribution of lidocaine in vivo, true kinetics of drug/neural tissue interactions must be studied in the absence of those confounding factors.

Lidocaine enters a nerve by a process other than free diffusion, through an epineurial sheath that is a slight obstacle. Given the rapid entry in vitro compared with the much smaller and transient content measured in vivo, it seems highly unlikely that lidocaine equilibrates with the nerve during a peripheral blockade.

Uptake: Ensheathed or desheathed isolated rat sciatic nerves were exposed to [(14)C]-lidocaine for 0 to 180 minutes and then removed and the lidocaine content of nerve and sheath analyzed. Washout: Isolated nerves were soaked in [(14)C]-lidocaine for 60 minutes and then placed in lidocaine-free solution for 0 to 30 minutes, with samples removed at different times to assess the drug content. Experimental variables included the effects of the ensheathing epineurium, lidocaine concentration, pH, presence of CO(2)-bicarbonate, and incubation duration.

The equilibrium uptake of lidocaine increased with incubation time, concentration, and the fraction of molecules in the nonionized form. The uptake rate was unaffected by drug concentration, but was about halved by the presence of the epineurial sheath, with the washout rate slowed less. Slight alkalinization, from pH 6.8 to pH 7.4, by bicarbonate-CO(2) buffer or a nonbicarbonate buffer, enhanced the neural uptake, and to the same degree. The washout of lidocaine was faster after shorter incubations at high concentrations than when equal amounts of lidocaine were taken up after long incubations at low lidocaine concentrations.