AIMTo study the cutaneous permeation kinetics and pharmacodynamics of lidocaine gel.

METHODSThe concentration of lidocaine in dermis following topical application in rats was determined by the cutaneous microdialysis technique and related parameters were calculated; the pharmacodynamics of the gel was evaluated by electric stimulation method with EMLA (eutectic mixture of local anesthetics) cream as a control.

RESULTSThe peak of percutaneous absorption kinetic profile of lidocaine gel across rat skin occurred at 1.25 h; the onset time of local anesthetic action of lidociane gel was similar to that of EMLA, but both the duration and depth of anesthetic effect were superior to EMLA cream.

CONCLUSIONLidocaine gel showed good anesthetic effect. The minimum effective concentration of lidocaine in dermis is 12 mg.L-1.

Anesthesia, Local ; Anesthetics, Local ; pharmacokinetics ; pharmacology ; Animals ; Gels ; Lidocaine ; pharmacokinetics ; pharmacology ; Male ; Pain Threshold ; drug effects ; Prilocaine ; pharmacokinetics ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Skin Absorption

AIMTo examine the quantitative relationship between solution specific conductivity and the permeability of tetracaine HCl, and to investigate the effect of receptor solution specific conductivity on the iontophoretic transport.

METHODSAn in vitro study was carried out to determine the iontophoretic permeability of tetracaine hydrochloride through rat skin. Iontophoretic flux of tetracaine hydrochloride through excised rat skin was determined using Valia-Chien two-chamber diffusion cells with a constant d.c. current and Ag/AgCl electrodes. The specific conductivities of donor and receptor solution were also measured.

RESULTSIontophoretic flux of tetracaine hydrochloride increased with a decrease of anion (chloride ion) concentration in receptor. And the iontophoretic permeability (ER, ER is the enhancement ratio, and ER = iontophoretic flux/passive flux) for tetracaine hydrochloride was directly related to the conductivity of receptor solution when other conditions were held constant. Linear regressions confirmed that ER was related to inverse of overall specific conductivity of donor and receptor solution [1/(ks.d + ks.r), ks.d and ks.r are the specific conductivity of donor and receptor solution].

CONCLUSIONThe results suggest that specific conductivity of receptor solution may be a important factor for the iontophoretic permeability of a solute.

Administration, Cutaneous ; Anesthetics, Local ; administration & dosage ; pharmacokinetics ; Animals ; Iontophoresis ; Male ; Rats ; Rats, Sprague-Dawley ; Skin Absorption ; Tetracaine ; administration & dosage ; pharmacokinetics

AIMTo study the effect of lidocaine-dodecanol binary eutectic system on the transdermal permeation of lidocaine.

METHODSBinary eutectic mixture of different proportions of lidocaine and dodecanol were prepared and the patch containing the binary eutectic mixture was developed. The solubilities of pure lidocaine and lidocaine from the binary eutectic system were determined in pH 7.9 phosphate buffer. The transdermal flux of lidocaine from the patches containing the binary eutectic system and pure lidocaine were measured using Franz-type single diffusion cell.

RESULTSThe melting point of the lidocaine-dodecanol binary eutectic system was markedly lower than that of pure lidocaine. The steady state transdermal flux of lidocaine from the patch of the binary eutectic system was six times as much as that of pure lidocaine patch.

CONCLUSIONThe lidocaine-dodecanol binary eutectic system could produce high thermodynamic activity of the drug and the high driving force for transdermal permeation of lidocaine.

Administration, Cutaneous ; Anesthetics, Local ; administration & dosage ; pharmacokinetics ; Animals ; Dodecanol ; administration & dosage ; chemistry ; Drug Combinations ; Drug Stability ; Guinea Pigs ; Lidocaine ; administration & dosage ; pharmacokinetics ; Skin Absorption ; Solubility

The volumetric caudal epidural steroid injection has been advocated to facilitate the delivery of medications to the lesion site. This study was aimed to examine the actual spreading patterns of this technique, using epidurogram. A total of 32 patients with chronic low back pain accompanied by radiculopathy of various causes (degenerative spondylosis, herniated nucleus pulposus, spondylolisthesis, and spinal stenosis) were included. The volumetric caudal epidural injection of the 10 mL mixture of contrast medium 5 mL, 0.5% bupivacaine 1 mL, triamcinolone 1.5 mL (60 mg) and normal saline 25 mL was performed. Immediately after the cessation of the first spread, the subsequent solution of another 10 mL of contrast medium 5 mL, 0.5% bupivacaine 1 mL and normal saline 4 mL was injected. This procedure was repeated serially until the total volume to be 50 mL. Continuous fluoroscopic imaging was obtained after each injection. Average time taken to complete the study was 37 sec per every 10 mL. The spreading levels of the mixture were distributed mainly at mid to lower lumbar area in the majority of the patients. During the subsequent injections, the levels were not changed significantly. This was thought to be due to the minimal resistance in cephalad direction, anatomic variations and Starling effect of epidural space.
Adult ; Aged ; *Anesthesia, Epidural ; Anesthetics, Local/*pharmacokinetics ; Bupivacaine/*pharmacokinetics ; Chronic Disease ; Female ; Fluoroscopy ; Glucocorticoids, Synthetic/pharmacokinetics ; Human ; Low Back Pain/*drug therapy ; Male ; Middle Age ; Spinal Diseases/drug therapy ; Triamcinolone/pharmacokinetics

OBJECTIVETo investigate the pharmacokinetics and pharmacodynamics of poly (lactide-co-glycolide) microspheres containing ropivacaine and dexamethasone for sciatic nerve block in mice.

METHODSA total of 165 female mice were randomly assigned into 3 groups, namely dexamethasone-loaded ropivacaine microsphere group (group A, n=55), ropivacaine microsphere group (group B, n=55) and PLGA microsphere group (group C, n=55). The mice received surgical implantation of the corresponding preparations near the sciatic nerve at the dose of 400 mg/kg. Hot plate test was used to evaluate the anesthetic effect of these microspheres at different time points after the implantation, and high-performance liquid chromatography (HPLC) was employed to determine plasma ropivacaine concentration.

RESULTSPharmacodynamic study showed that the duration of sciatic nerve sensory block was significantly longer in group A than in group B (P<0.05). The analysis of pharmacokinetics variables demonstrated that T(1/2) in group A was prolonged as compared with that of group B. No anesthetic effect was observed in group C.

CONCLUSIONDexamethasone-loaded ropivacaine microspheres can significantly prolong the analgesic effect of ropivacaine in mice.

Amides ; pharmacokinetics ; pharmacology ; Anesthetics, Local ; pharmacokinetics ; pharmacology ; Animals ; Delayed-Action Preparations ; Dexamethasone ; pharmacokinetics ; pharmacology ; Female ; Lactic Acid ; chemistry ; Mice ; Microspheres ; Nerve Block ; methods ; Polyglycolic Acid ; chemistry ; Random Allocation ; Sciatic Nerve

OBJECTIVETo prepare a new dental topical anesthetics, lidocaine hydrochloride loaded trans-activator of transcription peptide conjugated nano-niosome (LID-TAT-N), and to evaluate its transdermal properties and topical anesthesia effects.

METHODSLID-TAT-N was prepared using reverse-phase evaporation method, and lidocaine loaded conventional liposome (LID-CL) was prepared in the same manner as positive control. The diameter, ζ potential and encapsulation efficiency of LID-TAT-N and LID-CL were measured. The skin permeation of LID-TAT-N was examined, and compared with LID-CL and lidocaine injection (LID-IJ, as negative control), using a Franz diffusion cell mounted with depilated mouse skin in vitro for 12 hours. Each experiment was repeated six times. The anesthetic effect of the new topical anesthetic was investigated on the cornea of rabbits.

RESULTSThe mean diameter of LID-TAT-N was smaller than that of LID-CL [(152.7 ± 10.6) nm vs. (259.5 ± 15.5) nm, P < 0.01]. The 12 h cumulative permeation amount was significantly higher in LID-TAT-N group [(1 340.0 ± 97.5) µg · cm(-2)] than those of LID-CL and LID-IJ groups [(1 060.6 ± 80.2), (282.6 ± 65.1) µg · cm(-2), respectively, P < 0.05]. Rabbit corneal reflex results showed that LID-TAT-N had anesthetic effect and the duration of analgesia [(24.8 ± 2.8) min] was also longer than that of LID-IJ [(14.5 ± 2.3) min, P < 0.05].

CONCLUSIONSLID-TAT-N had good transdermal ability, and the advanced skin penetration feature can improve its tropical anesthetic effect.

Administration, Cutaneous ; Anesthesia, Dental ; Anesthetics, Local ; administration & dosage ; pharmacokinetics ; Animals ; Blinking ; drug effects ; physiology ; Cornea ; drug effects ; physiology ; Lidocaine ; administration & dosage ; pharmacokinetics ; Liposomes ; Mice ; Nanoconjugates ; administration & dosage ; chemistry ; Peptides ; Rabbits ; Skin ; metabolism ; Skin Absorption ; Trans-Activators ; administration & dosage ; chemistry ; pharmacokinetics

OBJECTIVE: To establish the models of postmortem redistribution(PMR) in dogs with epidural anesthesia and to investigate the effect of temperature on the PMR of Bupivacaine. METHODS: Eighteen male dogs were executed by epidural anesthesia with a dose of 5 mg/kg bupivacaine hydrochloride and randomly divided into three groups, room temperature (20-23 degrees C) group, 4 degrees C group and -20 degrees C group. The cardiac blood, peripheral blood, liver and cerebrum were collected at 0, 2, 4, 8, 24, 48, 72, 96, 120h postmortem. The contents of bupivacaine in those samples were analyzed by GC-NPD and GC-MS, the difference among three groups were compared. RESULTS: The bupivacaine PMR of room temperature group was evident and complex in cardiac blood, peripheral blood and cerebrum. The PMR of 4 degrees C group was weaker and slower than that of normal temperature group. The bupivacaine PMR of the -20 degrees C group was the weakest in three groups. CONCLUSION PMR of bupivacaine will happen in epidural anesthesia death dogs, but it could be delayed or prevent by low temperature storage.
Analgesia, Epidural ; Anesthetics, Local/pharmacokinetics* ; Animals ; Brain/metabolism* ; Bupivacaine/pharmacokinetics* ; Dogs ; Forensic Toxicology ; Gas Chromatography-Mass Spectrometry/methods* ; Liver/metabolism* ; Male ; Models, Animal ; Postmortem Changes ; Temperature ; Time Factors ; Tissue Distribution