Disease relevance of C07887

• In a clinical study involving 88 patients who received either drug, intraoperative hypotension was the most commonly reported adverse event with levobupivacaine and no serious arrhythmias occurred [1].
• The most common adverse event associated with levobupivacaine treatment was hypotension (31%) [2].
• Cardiac and CNS toxicity of levobupivacaine: strengths of evidence for advantage over bupivacaine [3].
• In contrast, in anaesthetised dogs no differences were seen in the incidence of spontaneous or electrical stimulation- induced ventricular tachycardia and fibrillations among animals exposed to levobupivacaine or bupivacaine [3].
• Thirteen of 19 animals died of ventricular fibrillation: four of six with bupivacaine (mean+/-s.e.mean actual fatal dose: 21.8+/-6.4 micromol), five of seven with levobupivacaine (22.9+/-3.5 micromol), four of six with ropivacaine (22.9+/-5.9 micromol) [4].

Psychiatry related information on C07887

• When considering levobupivacaine and ropivacaine for brachial plexus anesthesia, levobupivacaine should be considered when postoperative analgesia is a concern but not when an early return of motor activity is required [5].

High impact information on C07887

• While all local anaesthetics can cause direct negative inotropic effects, ropivacaine and levobupivacaine are less cardiotoxic than bupivacaine judging by the larger doses tolerated in laboratory animal preparations before the onset of serious cardiotoxicity (particularly electro-mechanical dissociation or malignant ventricular arrhythmias) [6].
• The tolerability profiles of levobupivacaine and bupivacaine were very similar in clinical trials [2].
• 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 [2].
• Stereoselective differences have been observed between the 2 enantiomers and the racemic mixture, with levobupivacaine exhibiting a slightly higher degree of plasma protein binding, a lower volume of distribution, a higher plasma clearance, and a shorter t 1/2 beta than the R-(+)-enantiomer [7].
• In experiment 2, colorectal distension-induced response in heart rate was less depressed in rats given levobupivacaine than in those given the other anesthetics [8].

Chemical compound and disease context of C07887

• BACKGROUND: Previous preclinical safety studies in ewes have found intravenous levobupivacaine and ropivacaine to be less potent toward causing central nervous system (CNS) and cardiac toxicity than bupivacaine [9].
• Fifteen minutes after the start of the dexmedetomidine infusion, continuous infusion of bupivacaine (Groups BC, BS, and BL) or levobupivacaine (Groups LC, LS, and LL) at 1 mg x kg(-1) x min(-1) was started and continued until tonic/clonic convulsions occurred [10].
• Safety and efficacy of levobupivacaine for postoperative pain relief after the surgical removal of impacted third molars: a comparison with lignocaine and adrenaline [11].
• METHODS: Ninety ASA I-II children between 1 and 7 years old, scheduled for inguinal hernia repair or orchidopexy under propofol anesthesia were randomized to receive a caudal block with 1 ml x kg(-1) of 0.2% bupivacaine, 0.2% ropivacaine or 0.2% levobupivacaine [12].

Biological context of C07887

• Therefore, the authors investigated the efficacy, safety, and pharmacokinetics of perioperative epidural levobupivacaine with and without fentanyl in children [13].
• RESULTS: Bupivacaine inhibited the activities of cardiac KATP channels (IC50 = 52 microm) stereoselectively (levobupivacaine, IC50 = 168 microm; ropivacaine, IC50 = 249 microm) [14].
• We investigated the effect of age on the absorption and disposition kinetics and the neural block characteristics after epidural administration of levobupivacaine 0.75% [15].
• Higher doses caused net vasodilatation, and the levobupivacaine responses were generally lower than the corresponding bupivacaine responses (P=0.022) [16].
• The efficacy and safety of three concentrations of levobupivacaine administered as a continuous epidural infusion in patients undergoing orthopedic surgery [17].

Anatomical context of C07887

• Central nervous system side effects were absent in volunteers given levobupivacaine, but five of eight volunteers given lidocaine experienced mild side effects [18].
• After release of the tourniquet, return of sensation to TES, pinprick (ulnar nerve), and return of motor function occurred later with levobupivacaine at median 25, 15, and 21.25 versus 10, 4.5, and 10 min with lidocaine [18].
• The authors undertook this investigation to determine if clinically relevant concentrations of bupivacaine and levobupivacaine interfere with exocytotic norepinephrine release from cardiac sympathetic nerve endings [19].
• Effects of levobupivacaine and ropivacaine on rat sciatic nerve blood flow [20].
• IMPLICATIONS: Postoperative epidural infusion of levobupivacaine can provide safe and effective analgesia for patients having hip or knee joint replacement [17].

Associations of C07887 with other chemical compounds

• BACKGROUND: The study was designed to determine and compare the median effective doses (MEDs) of intrathecal ropivacaine with levobupivacaine for labor analgesia [21].
• Levobupivacaine 0.125% and lidocaine 0.5% for intravenous regional anesthesia in volunteers [18].
• IMPLICATIONS: Sciatic nerve block using the infragluteal-parabiceps approach produces sensory loss and motor paralysis after a single 0.4 mL/kg injection of levobupivacaine 0.625% with epinephrine (1:200,000) in >90% of patients [22].
• We conclude that the epidural administration of a combination of levobupivacaine plus clonidine is well tolerated and gives better analgesia than either drug used alone [23].
• We compared the neurotoxic profile of racemic bupivacaine and levobupivacaine in: (i) a mouse model of N-methyl-D-aspartate (NMDA)-induced seizures and (ii) in an in vitro model of excitotoxic cell death [24].

Gene context of C07887

• RESULTS: The amide local anaesthetics bupivacaine, levobupivacaine and ropivacaine inhibited HERG channels at toxicologically relevant concentrations, with IC(50) values of 20 (SEM 2) micro M (n=29), 10 (1) micro M (n=40) and 20 (2) micro M (n=49), respectively [25].
• CONCLUSIONS: Clearance in infants is approximately half that described in adults, suggesting immaturity of P450 CYP3A4 and CYP1A2 enzyme isoforms that metabolize levobupivacaine in infants [26].
• RESULTS: The MED for levobupivacaine was 1.07 mg (95% confidence interval, 0.88-1.25 mg), and the MED for ropivacaine was 1.40 mg (95% confidence interval, 1.20-1.61 mg) [21].
• For example, in the 12-mg groups of levobupivacaine versus bupivacaine, mean duration of tolerance to transcutaneous electrical stimulation at T12 was 100 min for both [27].
• The time to onset of adequate sensory block (T10 dermatome) was similar in both treatment groups (13.6 +/- 5.6 min for levobupivacaine and 14.0 +/- 9.9 min for bupivacaine), with an average peak block height of T5 reached at 24.3 +/- 9.4 and 26.5 +/- 13.2 min, respectively [28].

Analytical, diagnostic and therapeutic context of C07887

• Fewer changes indicative of CNS depression on EEG were evident with levobupivacaine [2].
• At doses of 2.5 mg or greater, there was no significant difference in duration of analgesia between levobupivacaine (median, 63.5 min; range, 46-123 min) and ropivacaine (median, 59.0 min; range, 47-93 min; P = 0.18) [21].
• Relative analgesic potencies of levobupivacaine and ropivacaine for epidural analgesia in labor [29].
• METHODS: In this double-blind study, 100 parturients in early labor were randomized to receive either intrathecal ropivacaine or levobupivacaine [21].
• METHODS: After a control period, pregnant ewes that were fitted with instruments for long-term monitoring were randomized to receive a two-step intravenous infusion of levobupivacaine, bupivacaine, or ropivacaine, in a blinded manner, for 1 h [30].

References