title: Kinetics of uptake and washout of lidocaine in rat sciatic nerve in vitro.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Pain Research Center, MRB 611/BWH, 75 Francis Street, Boston, MA 02115-6110, USA.
authors: Stanley
authors: S
authors: Leeson
authors: Gary
authors: G
authors: Strichartz
mesh_terms: D000779:Anesthetics, Local / Q000493:pharmacokinetics*; D000818:Animals; D007700:Kinetics; D008012:Lidocaine / Q000493:pharmacokinetics*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D008012:Lidocaine
references: J Anat. 1963 Jan;97:35-44
references: 13981107
references: Anesthesiology. 1975 Jun;42(6):731-6
references: 1130741
references: Anesthesiology. 1985 Feb;62(2):141-4
references: 3970363
references: J Pharmacol Exp Ther. 1994 Oct;271(1):220-8
references: 7965718
references: Trans N Y Acad Sci. 1968 Jun;30(8):1082-92
references: 5250162
references: Reg Anesth. 1989 Nov-Dec;14(6):265-70
references: 2562097
references: Anesth Analg. 1987 Feb;66(2):159-65
references: 3813059
references: J Gen Physiol. 1973 Jul;62(1):37-57
references: 4541340
references: Anesthesiology. 1978 Apr;48(4):263-6
references: 637334
references: Anesth Analg. 1990 Aug;71(2):158-70
references: 2375517
references: J Pharmacol Exp Ther. 1997 Aug;282(2):802-11
references: 9262344
references: Anesth Analg. 2006 Jan;102(1):248-57
references: 16368838
references: Anesthesiology. 1995 Apr;82(4):1013-25
references: 7717536
references: Br J Anaesth. 1986 Mar;58(3):310-4
references: 3947493
references: Reg Anesth Pain Med. 2012 Jul-Aug;37(4):363-5
references: 22683708
references: Anesthesiology. 2000 Oct;93(4):1045-52
references: 11020760
references: Reg Anesth. 1997 Jul-Aug;22(4):363-71
references: 9223204
references: Anesth Analg. 1998 Feb;86(2):341-7
references: 9459246
references: Biochim Biophys Acta. 1986 Oct 9;861(2):368-72
references: 3019404
references: Anesth Analg. 1989 May;68(5):563-70
references: 2785778
references: J Pharmacol Exp Ther. 1970 Mar;172(1):1-17
references: 5416944
references: Anesthesiology. 2003 Jan;98(1):181-8
references: 12502995
references: J Gen Physiol. 1977 Apr;69(4):497-515
references: 300786
references: Anesth Analg. 1993 Jan;76(1):131-43
references: 8418714
references: Anesthesiology. 1995 Sep;83(3):583-92
references: 7661359
references: Anesthesiology. 2005 Nov;103(5):1035-45
references: 16249678
references: Anesthesiology. 2001 Dec;95(6):1441-54
references: 11748404
references: Biophys J. 2007 Jun 1;92(11):3988-4001
references: 17351014
references: Anesthesiology. 2003 Nov;99(5):1189-97
references: 14576558
references: Rev Physiol Biochem Pharmacol. 1977;79:1-50
references: 335473
references: J Anat. 1995 Feb;186 ( Pt 1):123-30
references: 7649808
references: Anesth Analg. 1987 Jan;66(1):9-17
references: 3099602