Ultralong peripheral nerve block by lidocaine:prilocaine 1:1 mixture in a lipid depot formulation: comparison of in vitro, in vivo, and effect kinetics.
BACKGROUND
The aim of this study was to develop stable and easily injectable lipid depot preparations of local anesthetics in which the drug concentration can be varied according to desired duration of action.


METHODS
The formulations contained a 2.0, 5.0, 10, 20, 40, 60, 80, or 100% eutectic mixture of lidocaine and prilocaine base in medium-chain triglyceride. Duration of sciatic nerve block and local neurotoxicity was investigated in rats with 2.0% lidocaine:prilocaine HCl solution and 99.5% ethanol as controls. The rate of release of local anesthetic from the site of administration and the possibility to predict in vivo depot characteristics from in vitro release data were investigated for the 20 and 60% formulations.


RESULTS
The duration of sensory sciatic block was prolonged 3 times with the 20% formulation and approximately 180 times with the 60% formulation, in comparison with the 2% aqueous solution. With the 80 and 100% formulations, all animals still showed nerve block after 2 weeks. The in vivo release of local anesthetic could be approximately predicted from in vitro data for the 20% but not for the 60% formulation. The formulations of 60% or greater and ethanol showed neurotoxic effects.


CONCLUSIONS
The pharmaceutical properties of these formulations compare favorably with those of other depot preparations. The high-percentage ones showed the longest duration of action yet reported for sciatic nerve block in rats. The possibility of using a high-concentration local anesthetic depot formulation as an alternative to ethanol or phenol for long-term nerve blocks in chronic pain merits further investigation.
Söderberg
Lars
L
Hospital Pharmacy, Malmö University Hospital, Sweden.
Dyhre
Henrik
H
Roth
Bodil
B
Björkman
Sven
S
D000465:Algorithms; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D008012:Lidocaine / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D009407:Nerve Block; D010525:Peripheral Nerves; D011318:Prilocaine / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve
D000779:Anesthetics, Local; D003692:Delayed-Action Preparations; D011318:Prilocaine; D008012:Lidocaine