Basic & clinical pharmacology & toxicology
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Basic Clin. Pharmacol. Toxicol. · Mar 2013
Antihyperalgesic effect of the GABA(A) ligand clobazam in a neuropathic pain model in mice: a pharmacokinetic-pharmacodynamic study.
Facilitation of spinal GABAergic inhibition with benzodiazepines (BZDs) reverses pain sensitization in animals; however, the use of BZDs in man is limited by their sedative effect. The antihyperalgesic effects of GABA(A) agonists are mediated by GABA(A) receptors containing α2 subunits, whereas sedation is linked to α1 subunit-containing receptors. α2 and α3 selective GABA(A) receptor modulators have been tested in animals but are not yet available for use in human beings. Clobazam is a 1,5-BZD, which exhibits less cognitive side effects than other benzodiazepines. ⋯ Clobazam blood concentrations decreased rapidly, falling below the limit of detection at 120 min. after drug application. Its main metabolite, N-desmethyl-clobazam, showed more delayed and prolonged pharmacokinetics, partly explaining why antihyperalgesia persisted when clobazam was no longer detectable in the blood. Considering its therapeutic margin and its pharmacokinetic properties, clobazam would be a valuable compound to assess the role of the GABAergic pathway in pain transmission in human beings.
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Basic Clin. Pharmacol. Toxicol. · Mar 2013
Randomized Controlled TrialThe effects of lidocaine used in sciatic nerve on the pharmacodynamics and pharmacokinetics of ropivacaine in sciatic nerve combined with lumbar plexus blockade: a double-blind, randomized study.
In this controlled, randomized, double-blind study, we compared the pharmacodynamics and pharmacokinetics of ropivacaine and staged injection of lidocaine and ropivacaine in a combined lumbar plexus-sciatic nerve block. The experiment was performed in two parts: pharmacodynamics study (Group r, n = 20; Group lr, n = 20) and pharmacokinetics study (Group R, n = 10; Group LR, n = 10). The sciatic nerve blockade was performed using either (1) 10 mL of 2% lidocaine and then 10 mL of 0.75% ropivacaine (Group lr and Group LR) or (2) 10 mL of normal saline (N. ⋯ C(max) of ropivacaine in Group LR was significantly higher than that in Group R. A significant increase in AUC((0-t)) and AUC((0-∞)) was observed in Group LR compared with Group R. When 2% lidocaine and 0.75% ropivacaine are used for a combined sciatic nerve-lumbar plexus block by 'staged' injection, lidocaine induced faster onset times, decreased the block duration and increased the AUC and C(max) of ropivacaine.