Bupivacaine pharmacokinetics

D. J. Kopacz, C. M. Bernards, H. W. Allen, C. Landau, P. Nandy, D. Wu, and P. G. Lacouture. A model to evaluate the pharmacokinetic and pharmacodynamic variables of extended-release products using in vivo tissue microdialysis in humans Bupivacaine-loaded microcapsules. Anaesth. Analg. 97 124-131 (2003). 

The local anesthetics can be broadly categorized on the basis of the chemical nature of the linkage contained within the intermediate alkyl chain group. The amide local anesthetics include lidocaine (7.5), mepivacaine (7.6), bupivacaine (7.7), etidocaine (7.8), prilocaine (7.9), and ropivacaine (7.10) the ester local anesthetics include cocaine (7.11), procaine (7.12), benzocaine (7.13), and tetracaine (7.14). Since the pharmacodynamic interaction of both amide and ester local anesthetics with the same Na" channel receptor is essentially idenhcal, the amide and ester functional groups are bioisosterically equivalent. However, amide and ester local anesthetics are not equal from a pharmacokinetic perspective. Since ester links are more susceptible to hydrolysis than amide links. 

Feldman HS, Dvoskin S, Halldin MH et al. (1997) Comparative anesthetic efficacy and pharmacokinetics of epidurally administered ropivacaine and bupivacaine in the sheep. Regional Anesthesia 22 451 160... 

Bupivacaine exhibits stereoselectivity of local anesthetic activity, CNS and cardiac toxicity and pharmacokinetics. /J-Bupivacaine is more potent, more toxic and more rapidly cleared than its 5-isomer. 

The interaction of itraconazole 200 mg orally od for 4 days with a single intravenous dose of racemic bupivacaine (0.3 mg /kg given over 60 minutes) has been examined in a placebo-controlled crossover study in 10 healthy volunteers (65). Itraconazole reduced the clearance of i -bupivacaine by 21% and that of 5-bupivacaine by 25%, but had no other significant effects on the pharmacokinetics of the enantiomers. Reduction of bupivacaine clearance by itraconazole is likely to increase steady-state concentrations of bupivacaine enantiomers by 20-25%, and this should be taken into account in the concomitant use of itraconazole and bupivacaine. 

Meunier JF, Goujard E, Dubousset AM, Samii K, Mazoit JX. Pharmacokinetics of bupivacaine after continuous epidural infusion in infants with and without biliary atresia. Anesthesiology 2001 95(l) 87-95. 

Pharmacokinetics of bupivacaine enantiomers after different modes of administration. 

Stereochemistry of the local anesthetics, however, plays an important role in their observed toxicity and pharmacokinetic properties. For example, ropivacaine and levobupivacaine, the only optically active local anesthetics currently being marketed, have considerably lower cardiac toxicities than their close structural analogue, bupivacaine (45). Furthermore, the degree of separation between motor and sensory blockade is more apparent with ropivacaine and levobupivacaine relative to bupivacaine at a lower end of the dosage scale (46). Thus, the observed cardiac toxicity of bupivacaine has been attributed to the F -( + )-bupivacaine enantiomer (41,42,43). The exact mechanisms for this enantiomeric... 

The stereoselective pharmacokinetics of prilocaine (Table 2) and bupivacaine enantiomers have been studied after intravenous doses [207, 208]. For both drugs, the R enantiomers are cleared more rapidly than the respective S enantiomers. The R S clearance ratios of both drugs lie between 1.25 and 1.34 [207,208]. 

Mather, L.E. McCall, P. McNicol, P.L. Bupivacaine enantiomer pharmacokinetics after intercostal neural blockade in liver transplantation patients. Anesth. Analg. 1995, 80, 328-335. 

A study on the use of chloroprocaine 3%, bupivacaine 0.5% or a mixture of chloroprocaine 1.5% with bupivacaine 0.375% in obstetric epidural anaesthesia found that time to onset of analgesia, time to maximum analgesia, and effectiveness of analgesia were similar irrespective of the treatment regimen. Bupivacaine 0.5% alone had a longer duration of action than chloroprocaine or the mixture of anaesthetics. Another study found that lidocaine did not affect the pharmacokinetics of bupivacaine. ... 

Freysz M, Beal JL, D Athis P, Mounie J, Wilkening M, Escousse A, Pharmacokinetics of bupivacaine after axillary brachial plexus block, IntJClin Pharmacol Ther Toxicol (1987) 25,392-5,... 

Pretreatment with eimetidine 300 mg intramuseularly 1 to 4 hours before epidural anaesthesia with 0.5% bupivaeaine (for eaesarean section) had no effect on the pharmacokinetics of bupivacaine in 16 women or their foetuses when compared with 20 control women, although the maternal unbound bupivacaine plasma levels rose by 22%. These findings were confirmed in two similar studies in which women were pretreated with cimetidine before caesarean section, and a further study in 7 healthy subjects (6 women and one man) given two oral doses of cimetidine 400 mg before intramuscular bupivacaine. However, the AUC of bupivacaine in 4 healthy male subjects was increased by 40% (when compared to placebo) by cimetidine 400 mg at 10 pm the previous evening and 8 am on the study day, followed by a 50-mg infusion of bupivacaine at 11 am. ... 

Drug interactions administration of DepoDur after an analgesic dose of bupivacaine (0.25% - 20 mL) increases peak serum concentrations of morphine. Increasing the interval between the analgesic dose and DepoDur administration to greater than 30 minutes minimizes this pharmacokinetic interaction. 

Cuvhlon P, NouveUon E, Ripart J, Boyer JC, Dehour L, Mahamat A, L hermite J, Boisson C, ViaUes N, Lefrant JY, de La Coussaye JE. A comparison of the pharmacodynamics and pharmacokinetics of bupivacaine, ropivacaine (with epinephrine) and their equal volume mixtures with lidocaine used for femoral and sciatic nerve blocks a double-blind randomized study. Anesth Analg 2009 108(2) 641-649. 

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