Levobupivacaine: a review of its pharmacology and use as a local anaesthetic.
Based on findings that the cardiotoxicity infrequently observed with racemic bupivacaine shows enantioselectivity, i.e. it is more pronounced with the R(+)-enantiomer, the S(-)-enantiomer (levobupivacaine) has been developed for clinical use as a long acting local anaesthetic. The majority of in vitro, in vivo and human pharmacodynamic studies of nerve block indicate that levobupivacaine has similar potency to bupivacaine. However, levobupivacaine had a lower risk of cardiovascular and CNS toxicity than bupivacaine in animal studies. In human volunteers, levobupivacaine had less of a negative inotropic effect and, at intravenous doses >75 mg, produced less prolongation of the QTc interval than bupivacaine. Fewer changes indicative of CNS depression on EEG were evident with levobupivacaine. Levobupivacaine is long acting with a dose-dependent duration of anaesthesia. The onset of action is < or = 15 minutes with various anaesthetic techniques. In studies of surgical anaesthesia in adults, levobupivacaine provided sensory block for up to 9 hours after epidural administration of < or = 202.5 mg, 6.5 hours after intrathecal 15 mg, and 17 hours after brachial plexus block with 2 mg/kg. Randomised, double-blind clinical studies established that the anaesthetic and/or analgesic effects of levobupivacaine were largely similar to those of bupivacaine at the same dose. Sensory block tended to be longer with levobupivacaine than bupivacaine, amounting to a difference of 23 to 45 minutes with epidural administration and approximately 2 hours with peripheral nerve block. With epidural administration, levobupivacaine produced less prolonged motor block than sensory block. This differential was not seen with peripheral nerve block. Conditions satisfactory for surgery and good pain management were achieved by use of local infiltration or peribulbar administration of levobupivacaine. Levobupivacaine was generally as effective as bupivacaine for pain management during labour, and was effective for the management of postoperative pain, especially when combined with clonidine, morphine or fentanyl. The tolerability profiles of levobupivacaine and bupivacaine were very similar in clinical trials. No clinically significant ECG abnormalities or serious CNS events occurred with the doses used. The most common adverse event associated with levobupivacaine treatment was hypotension (31%).


CONCLUSIONS
Levobupivacaine is a long acting local anaesthetic with a clinical profile closely resembling that of bupivacaine. However, current preclinical safety and toxicity data show an advantage for levobupivacaine over bupivacaine. Clinical data comparing levobupivacaine with ropivacaine are needed before the role of the drug can be fully established. Excluding pharmacoeconomic considerations, levobupivacaine is an appropriate choice for use in place of bupivacaine.
Foster
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Adis International Limited, Mairangi Bay, Auckland, New Zealand. demail@adis.co.nz
Markham
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D000328:Adult; D000773:Anesthesia, Obstetrical; D000775:Anesthesia, Spinal; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D019540:Area Under Curve; D002045:Bupivacaine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D002319:Cardiovascular System / Q000187:drug effects; D004361:Drug Tolerance; D005260:Female; D006207:Half-Life; D006801:Humans; D009407:Nerve Block; D010149:Postoperative Pain / Q000188:drug therapy; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000779:Anesthetics, Local; D002045:Bupivacaine