Levobupivacaine Hydrochloride

Levobupivacaine hydrochloride is a long-acting local anaesthetic developed as the S(-)-enantiomer of racemic bupivacaine to reduce cardiovascular and central nervous system toxicity. The mechanism of action involves reversible binding to voltage-gated sodium channels, modulating ionic flux and preventing the initiation and transmission of nerve impulses by stabilizing the neuronal membrane. In vitro, in vivo and human pharmacodynamic studies indicate that levobupivacaine has similar potency to bupivacaine for nerve block, while animal studies demonstrate a lower risk of cardiovascular and CNS toxicity.
In human volunteers, levobupivacaine produces less negative inotropic effect and less QTc interval prolongation than bupivacaine at intravenous doses above 75 mg. The onset of action is within 15 minutes, with dose-dependent duration of anaesthesia providing sensory block for up to 9 hours after epidural administration, 6.5 hours after intrathecal injection and 17 hours after brachial plexus block. Sensory block tends to be longer with levobupivacaine than bupivacaine, while motor block is less prolonged than sensory block with epidural administration.

Fig. 1 Mean duration of sensory and motor block with levobupivacaine compared with bupivacaine for ulnar nerve blockade. (Foster R H, Markham A. 2000)

Levobupivacaine hydrochloride-loaded PLGA nanospheres with drug loading of 29.13 percent, encapsulation efficiency of 87.09 percent and average particle size of 81.43 micrometers were prepared by solvent evaporation methodology. Subcutaneous and subarachnoid administration of the nanospheres in rabbits produced two concentration peaks in blood with lower peak concentrations and longer average residence time compared to raw drug. The LevoBPV Hcl/PLGA group showed increased diameter and area of the basilar artery, higher neuronal density, reduced neuronal apoptosis rate, elevated levels of SOD, GSH-Px and NO in cerebrospinal fluid, and decreased levels of MDA and ET-1 versus the raw drug group. These nanospheres inhibited neuronal apoptosis following subarachnoid hemorrhage, regulated oxidative stress and vasoconstrictor factor expression, thereby suppressing delayed cerebral vasospasm and alleviating brain tissue damage.