Levobupivacaine hydrochloride
[CAS# 27262-48-2]

Identification

• Classification: Biochemical >> Inhibitor >> Transmembrane transporters >> Sodium channel inhibitor
• Name: Levobupivacaine hydrochloride
• Synonyms: S-(-)-1-Butyl-2',6'-pipecoloxylidide hydrochloride
• Protein Sequence: X
• Molecular Formula: C₁₈H₂₈N₂O^.HCl
• Molecular Weight: 324.89
• CAS Registry Number: 27262-48-2
• EC Number: 690-037-4
• SMILES: CCCCN1CCCC[C@H]1C(=O)NC2=C(C=CC=C2C)C.Cl

Properties

• Solubility: DMSO 47mg/mL (Expl.)
• alpha: -12.5 º (c=2, water)

Safety Data

• Hazard Symbols: GHS06;GHS07 Danger
• Hazard Statements: H300-H310-H315-H319-H330-H335
• Precautionary Statements: P260-P261-P262-P264-P264+P265-P270-P271-P280-P284-P301+P316-P302+P352-P304+P340-P305+P351+P338-P316-P319-P320-P321-P330-P332+P317-P337+P317-P361+P364-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	2	H310
Acute toxicity	Acute Tox.	2	H300
Acute toxicity	Acute Tox.	1	H330

Discovory and Applicatios

Levobupivacaine hydrochloride is the S-enantiomer of bupivacaine and belongs to the amide class of local anesthetics. It is used to produce regional anesthesia and analgesia by blocking voltage-gated sodium channels in nerve membranes, which inhibits nerve impulse conduction and results in a reversible loss of sensation in the targeted area. Levobupivacaine hydrochloride is recognized for providing long-lasting anesthesia with a reduced risk of cardiotoxicity and central nervous system toxicity compared to the racemic mixture of bupivacaine.

Levobupivacaine was developed and introduced clinically in the late 1990s and early 2000s as an alternative to racemic bupivacaine, motivated by a desire to improve the safety profile of local anesthetics used in various regional anesthesia techniques. Being the pure S-enantiomer, levobupivacaine has a higher therapeutic index and lower affinity for cardiac sodium channels, which reduces the potential for adverse cardiovascular effects.

Pharmacodynamically, levobupivacaine exerts its anesthetic effect by reversible blockade of sodium ion influx through voltage-gated sodium channels, thereby preventing depolarization and propagation of nerve impulses. It is effective in different types of regional anesthesia, including epidural, spinal, peripheral nerve blocks, and infiltration anesthesia. The duration of anesthesia provided by levobupivacaine typically ranges from several hours to up to 8 hours depending on the dose, concentration, and administration route.

Levobupivacaine hydrochloride is typically supplied as a sterile solution for injection in concentrations such as 0.25%, 0.5%, and 0.75%, often used with or without vasoconstrictors like epinephrine to prolong its duration of action and reduce systemic absorption. It has a slower onset of action compared to some other local anesthetics but is valued for its prolonged analgesic effect and reduced toxicity.

Pharmacokinetically, levobupivacaine is absorbed from the site of administration into systemic circulation at rates dependent on the vascularity of the tissue. It is highly bound to plasma proteins, mainly alpha-1 acid glycoprotein, which influences its distribution and duration. Metabolism occurs primarily in the liver by cytochrome P450 enzymes to inactive metabolites, which are then excreted in the urine. The elimination half-life ranges from approximately 2.5 to 3.5 hours.

Clinically, levobupivacaine is indicated for surgical anesthesia and postoperative analgesia, as well as pain control in obstetrics and orthopedic surgeries. It has demonstrated comparable efficacy to racemic bupivacaine in providing sensory and motor blockade, while offering a safer profile in terms of cardiac and central nervous system side effects. This improved safety is especially important in patients with cardiovascular risk factors or when higher doses are required.

Adverse effects of levobupivacaine hydrochloride are consistent with those of local anesthetics and include central nervous system symptoms such as dizziness, tinnitus, or seizures in rare cases of systemic toxicity. Cardiovascular adverse effects are less frequent and less severe compared to racemic bupivacaine, but caution is still warranted. Proper dosing and administration technique are essential to minimize the risk of toxicity.

In summary, levobupivacaine hydrochloride is a long-acting, amide local anesthetic S-enantiomer with a favorable safety profile compared to racemic bupivacaine. It is widely used in regional anesthesia and analgesia for various surgical procedures, providing effective anesthesia with reduced cardiotoxicity and central nervous system adverse effects.

References

2004. Pharmacokinetics of levobupivacaine 0.25% following caudal administration in children under 2 years of age. British Journal of Anaesthesia, 92(2).
DOI: 10.1093/bja/aeh051

2023. Sustained release of levobupivacaine from temperature-sensitive injectable hydrogel for long-term local anesthesia in postoperative pain management. Biomaterials, 299.
DOI: 10.1016/j.biomaterials.2023.122129

2024. The impact of epidural ropivacaine versus levobupivacaine for labor analgesia on maternal and fetal outcomes: a meta-analysis. BMC Anesthesiology, 24(1).
DOI: 10.1186/s12871-024-02767-4