The Effect of pH on the Permeation of Lidocaine Hydrochloride Across Excised Rat Skin

The effect of pH on the permeation of Lidocaine hydrochloride (LH) across excised rat skin was studied, the steady state flux (JSS) at different pH being determined using improved Valia-Chien diffusion cells. JSS increased substantially when pH was close to the pKa of LH. The profile of JSS versus pH showed an 慡?shaped curve. JSS of Lidocaine free base (LFB) was fourteen times that of LH. The pH of vehicle influences the permeation of LH significantly and should be considered as an important factor when a formulation is developed.

Antitumor efficacy of lidamycin on hepatoma and active moiety of its molecule

AIM: To study the in vitro and in vivo antitumor effect of lidamycin (LDM) on hepatoma and the active moiety of its molecule.METHODS: MTT assay was used to determine the growth inhibition of human hepatoma BEL-7402 cells, SMMC-7721cells and mouse hepatoma H22 cells. The in vivo therapeutic effects of lidamycin and mitomycin C were determined by transplantable hepatoma 22 (H22) in mice and human hepatoma BEL-7402 xenografts in athymic mice.RESULTS: In terms of IC50values, the cytotoxicity of LDM was 10 000-fold more potent than that of mitomycin C (MMC)and adriamycin (ADM) in human hepatoma BEL-7402 cells and SMMC-7721 cells. LDM molecule consists of two moieties,an aproprotein (LDP) and an enediyne chromophore (LDC). In terms of IC50 values, the potency of LDC was similar to LDM. However, LDP was 105-fold less potent than LDM and LDC to hepatoma cells. For mouse hepatoma H22 cells, the IC50value of LDM was 0.025 nmol/L. Given by single intravenous injection at doses of 0.1, 0.05 and 0.025 mg/kg, LDM markedly suppressed the growth of hepatoma 22 in mice by 84.7%, 71.6% and 61.8%,respectively. The therapeutic indexes (TI) of LDM and MMC were 15 and 2.5, respectively. By 2 iv. Injections in two experiments, the growth inhibition rates by LDM at doses of 0.1, 0.05, 0.025, 0.00625 and 0.0125 mg/kg were 88.8-89.5%, 81.1-82.5%, 71.2-74.9%, 52.3-59.575%,and 33.3-48.3%, respectively. In comparison, MMC at doses of 5, 2.5, and 1.25 mg/kg inhibited tumor growth by 69.7-73.6%, 54.0-56.5%, and 31.5-52.2%,respectively. Moreover, in human hepatoma BEL-7402 xenografts, the growth inhibition rates by LDM at doses of 0.05 mg/kg ×2 and 0.025 mg/kg ×2 were 68.7%and 27.2%, respectively. However, MMC at the dose of 1.25 mg/kg ×2 showed an inhibition rate of 34.5%. The inhibition rate of tumor growth by LDM was higher than that by MMC at the tolerated dose.CONCLUSION: Both LDM and its chromophore LDC display extremely potent cytotoxicity to hepatoma cells. LDM shows a remarkable therapeutic efficacy against murine and human hepatomas in vivo.

Comparison of 1.5% lidocaine and 0.5% ropivacaine epidural anesthesia combined with propofol general anesthesia guided by bispectral index

Objective： To compare the effects of epidural anesthesia with 1.5% lidocaine and 0.5% ropivacaine on propofol requirements, the time to loss of consciousness （LOC）, effect-site propofol concentrations, and the hemodynamic variables during induction of general anesthesia guided by bispectral index （BIS） were studied. Methods： Forty-five patients were divided into three groups to receive epidurally administered saline （Group S）, 1.5% （w/w） lidocaine （Group L）, or 0,5% （w/w） ropivacaine （Group R） Propofol infusion was started to produce blood concentration of 4 lag/ml. Once the BIS value reached 40-50, endotracheal intubation was facilitated by 0.1 mg/kg vecuronium. Measurements included the time to LOC, effect-site propofol concentrations, total propofol dose, mean arterial blood pressure （MABP）, and heart rate （HR） at different study time points. Results： During induction of anesthesia, both Groups L and R were similar for the time to LOC, effect-site propofol concentrations, total propofol dose, MABP, HR, and BIS. The total doses of propofol administered until 1 min post-intubation were significantly less in patients of Groups R and L compared with Group S. MABP and HR were significantly lower following propofol induction compared with baseline values in the three groups, or MABP was significantly increased following intubation as compared with that prior to intubation in Group S but not in Groups R and L while HR was significantly increased following intubation in the three groups. Conclusion： Epidural anesthesia with 1.5% lidocaine and 0.5% ropivacaine has similar effects on the time to LOC, effect-site propofol concentrations, total propofol dose, and the hemodynamic variables during induction of general anesthesia.

Effect of diltiazem and lidocaine on arterial pressure or heart rate and the quality of extubation in patients undergoing uvulopalatopharyngoplasty

Objective：To evaluate the effect of diltiazem and lidocaine on arterial pressure or heart rate and the quality of extubation in patients undergoing uvulopalatopharyngoplasty. Methods： Sixty patients were randomly divided into 4 groups： In the control group patients were given saline; in the lidocaine group patients were given 1.0 mg/kg lidocaine ; in the diltiazem group patients were given 0. 2 mg/kg diltiazem; and in the lidocaine plus diltiazem group patients were given 1.0 mg/kg lidocaine and 0. 2 mg/kg diltiazem. These drugs were given 2 rain before tracheal extuhation. Values for SBP, DBP, and HR were recorded, on arriving at the operating room, immediately at the end of the surgery, at the time of injection of the study drugs, at tracheal extubation, at 1 min and 5 min after extubation. The quality of extubation according to the Sebel＇s grading scale were compared among the 4 groups. Results：During extubation in the control group HR, SBP and DBP increased significantly when compared to baseline levels. Both lidocaine （1.0 mg/kg） and diltiazem （0. 2 mg/kg） successfully alleviated these increases. The suppressive effect of diltiazem was greater than that of lidocaine. The combinative use of the two drugs minimized the increases. The administration of lidocaine significantly suppressed bucking or coughing compared with the other groups. Conclusions： The pressor responses and tachycardia occurring in patients with uvulopalatopharyngoplasty during emergence from anesthesia and tracheal extubation, can be easily blocked by a bolus dose of 1.0 mg/kg lidocaine, 0. 2 mg/kg diltiazem or the comhinative use of the two drugs. And the concurrent use of lidocaine and diltiazem alleviated the hemodynamic changes more obviously.

Effectiveness of Mesotherapy on Temporomandibular Joint Disorders

TMJDs （Temporomandibular joint disorders） are a common pathology but best treatment remains unclear. The goal of this study was to evaluate the effectiveness of mesotherapy on TMJD. We conducted a case review of all TMJD patients treated since 2006 with mesotherapy procedures only and using a cocktail of drugs composing of lidocaine, piroxicam and pentoxifylline. Patients were treated every 15 days until symptomatic relief was achieved and thereafter every two months. Main outcome was complete symptomatic relief, and associated factors were analysed. 27 patients were included. Complete pain relief was achieved in 26. The necessary number of procedures to get pain relief ranged from 1 to 6 （median of 1） and the total number of treatments from 1 to 40 （median of 11）. 19 patients had other painful complains mainly related with anxiety disorders. A weak correlation （r = 0.357; p = 0.05） between anxiety disorders and the required months of treatments was found. Mesotherapy is a valuable option on pain relief in a temporomandibular pain syndrome with none of the systemic effects of oral medication. Anxiety may have a role on the aetiology and therapeutic success highlights the holistic approach of these patients. Future comparative studies are necessary.

Different suppressive effect of lidocaine on persistent Na^+ current and transient Na^+ current in dorsal root ganglion neurons

Objective ：To investigate the different suppressive effect of lidocaine on persistent Na^＋ current and transient Na^＋ current in injured or uninjured dorsal root ganglion neurons. Methods： Totally 23 SD rats were randomly divided into 2 groups： control group （n： 10） and chronically compressed DRG （dorsal root ganglion） group （CCD group, n= 13）. Rats were anesthetized and DRG was isolated. Single DRG neuron was isolated by enzymatic disassociation method. Persistent Na^＋ current （INap） and transient Na^＋ current （INaT） were elicited in voltage clamp mode. Results： The presence of INap was testified in most DRG neurons （38/46 neurons in CCD group and 31/39 neurons in control group, P〉0. 05）. However, the cur- rent density of INap in CCD group （4. 6±0. 6 pA/pF, n=38 neurons） was greater than that in control group （2.5±0.4 pA/pF, n=31 neurons） （P〈0. 05）. The characteristics of INap was observed and found that INap could he blocked by 0.2 μmol/L tetrodotoxin easily. Furthermore, the does-effect relationship of lidocaine on INaP and IN.T were also examined. INaP and IN.T were suppressed by different concentrations of li- docaine, the range for INap was 5-20 μmol/L and for INaT was 0. 05-2 mmol/L. Conclusion： INap and INaT were suppressed by different concentrations of lidocaine. INap was suppressed by very low concentration of lidocaine （5-20 μmol/L）. However, INaT could only be blocked by high concentration of lidocaine （0.05-2 mmol/L）.

The effects of local anesthetics on intracellular Ca2+ release from ryanod ine-sensitive Ca2+ stores in gerbil hippocampal neurons

OBJECTIVE: To examine the effects of procaine and lidocaine on intracellular Ca(2+) release from sarcoplasmic reticulum ryanodine-sensitive Ca(2+) stores. METHODS: The experiment was performed on hippocampal slices from 60-80 g male Mongolian gerbils. Levels of intracellular Ca(2+) concentration in the slices were measured by microfluorometry. The slices were perfused with 50 mmol/L KCl containing medium for 30 seconds. Then, the medium was switched to physiological medium. After 5 min of incubation, the slice was perfused with 20 mmol/L caffeine containing physiology medium for 2 min. Following incubation, the slice was superfused with physiological medium until the end of the experiment. The effects of procaine and lidocanin (100 micro mol/L) on caffeine-evoked Ca(2+) release were evaluated by adding them to the medium after high K(+) medium perfusion. RESULTS: Caffeine induced a marked increase in intracellular Ca(2+) concentration which was then decreased 12% upon the addition of procaine (P

The effects of local anesthetics on intracellular Ca^(2+) release from ryanodine-sensitive Ca^(2+) stores in gerbil hippocampal neurons

To examine the effects of procaine and lidocaine on intracellular Ca 2+ release from sarcoplasmic reticulum ryanodine sensitive Ca 2+ stores Methods The experiment was performed on hippocampal slices from 60-80 g male Mongolian gerbils Levels of intracellular Ca 2+ concentration in the slices were measured by microfluorometry The slices were perfused with 50 mmol/L KCl containing medium for 30 seconds Then, the medium was switched to physiological medium After 5 min of incubation, the slice was perfused with 20 mmol/L caffeine containing physiology medium for 2 min Following incubation, the slice was superfused with physiological medium until the end of the experiment The effects of procaine and lidocanin (100 μmol/L) on caffeine evoked Ca 2+ release were evaluated by adding them to the medium after high K + medium perfusion Results Caffeine induced a marked increase in intracellular Ca 2+ concentration which was then decreased 12% upon the addition of procaine ( P 【0 05); however, lidocaine, did not induce a similar inhibitory reaction Conclusion Procaine inhibits ryanodine receptor mediated Ca 2+ release from intracellular Ca 2+ stores, while lidocaine may inhibit Ca 2+ release through other mechanisms

Efficacy of amiodarone and lidocaine for preventing ventricular fibrillation after aortic cross-clamp release in open heart surgery:a meta-analysis of randomized controlled trials

Objective： The relative preventative efficacy of amiodarone and lidocaine for ventricular fibrillation（VF） after release of an aortic cross-clamp（ACC） during open heart surgery has not been determined. This meta-analysis was designed to systematically evaluate the influence of amiodarone, lidocaine, or placebo on the incidence of VF after ACC. Methods： Prospective randomized controlled trials（RCTs） that compared the VF-preventative effects of amiodarone with lidocaine, or amiodarone or lidocaine with placebo were included. Pub Med, EMBASE, and the Cochrane Library were searched for relevant RCTs. Fixed or randomized effect models were applied according to the heterogeneity of the data from the selected studies. Results： We included eight RCTs in the analysis. Pooled results suggested that the preventative effects of amiodarone and lidocaine were comparable（relative risk（RR）=1.12, 95% confidence interval（CI）： 0.70 to 1.80, P=0.63）, but both were superior to the placebo（amiodarone, RR=0.71, 95% CI： 0.51 to 1.00, P=0.05; lidocaine, RR=0.63, 95% CI： 0.46 to 0.88, P=0.006）. The percentage of patients requiring electric defibrillation counter shocks（DCSs） did not differ significantly among patients administered amiodarone（RR=0.21, 95% CI： 0.04 to 1.19, P=0.08）, lidocaine（RR=2.44, 95% CI： 0.13 to 44.02, P=0.55）, or the placebo（RR=0.56, 95% CI： 0.25 to 1.25, P=0.16）. Conclusions： Amiodarone and lidocaine are comparably effective in preventing VF after ACC, but the percentage of patients who subsequently require DCSs does not differ among those administered amiodarone, lidocaine, or placebo.

Study on solubility improvement of lidocaine by ternary solid dispersion

In the present study,we aimed to probe the possibility of using mixed poloxamers as carriers to prepare ternary solid dispersion(SD)that facilitated solubility and dissolution rate of the poorly water soluble drug and compare with binary SD with single poloxamer.Lidocaine(LIC)was selected as a model drug,and poloxamer 188(P188)and poloxamer 407(P407)were utilized as single and mixed carriers.Depending on DSC and the dissolution testing,the appropriate ratio of SD prepared by melting method was optimized.Ternary and binary SD was characterized by DSC,XRD,SEM and FTIR.In vitro dissolution study,phase solubility study and saturated solubility study were performed to clarify solubilization from apparent phenomena and inherent reason.Moreover,stability study under different relative humidity(RH)was investigated.Physical characterizations of binary and ternary SD exhibited the formation of eutectic mixture and the presence of molecular interaction.Compared with the pure LIC,the dissolution rate and solubility of LIC in binary and ternary SDs were enhanced.The phase solubility study revealed an AL-type curve.Furthermore,the stability test indicated that ternary and binary SD was stable.The results of this study demonstrated that SD with mixed poloxamers could improve dissolution rate and solubility of poorly water-soluble drug.