Effects Stability Of Alkalinization Of Lidocaine In Patients With Surface Anesthesia Of Urethra And Pharmacokinetics

Objectives: Detect the stability of carbonated lidocaine gel; evaluate thesurface anesthetic potency of the gel for cystoscopy in male patient; measureplasma lidocaine concentration in order to assess the efficiency and safety ofthe carbonated gel for surface anesthesia in male adult urethra.Methods: Part I:0ml,0.5ml,1ml,1.5ml,2ml, and2.5ml of5%sodium bicarbonate were added to10ml of2%lidocaine gel gradually, the pHvalue was detected with pH meter. The gel with different pH was kept at roomtemperature for90days, and soluble lidocaine in the gel was measured byusing high performance liquid chromatography in0,1,7,14,30,60, and90days. Part II: sixty ASAⅠorⅡmales patients, aged25～55years, weighing45～78kg, scheduled for cystoscopy were randomized into two groups, eachgroup consist30patients. Patients with liver disease, kidney disease or historyof allergic to lidocaine were excluded. The patients did not take any analgesicagents for at least3days before the test.10ml of2%lidecaine gel+1ml of0.9%sodium chloride (Group L) or+1ml of5%sodium bicarbonate (groupN) was slowly intra-urethral injected. After5minutes occlusion of the urethrato prevent leakage, cystoscopy was started and the pain response was assessedby VAS. The first attempt insertion success rate was recorded, and the patientswere asked whether they still fear of such procedure. Part Ⅲ: Twenty ASAⅠorⅡmales patients, aged25～55years, weighing45～75kg, undergoingsurgical operation were randomized into two groups, each group consist10patients. Patients with liver disease, kidney disease or history of allergic tolidocaine were excluded. Four mililiter of venous blood was taken before andat1,3,5,10,20,40and80min after the lidocaine gel were delivered as inPart II. Plasma lidocaine concentrations was measured with high performanceliquid chromatography-mass spectrometry. Results: Part I: The alkalized lidocaine gel was stable when the pH waslower than7.20, Compared with pH value of lidocaine gel6.37, pH7.33fromthe7th day and pH7.44from1th day the lidocaine concentrations wassignificantly decreased（P＜0.05）,but there were no significant differences inpH6.37,7.12and7.20. Part Ⅱ: There were no significant differences in thephysical characteristics of patients between the two groups（P＞0.05）; Asignificantly lower VAS was seen in group N; The first attempt insertionsuccess rate in Group N was significantly higher than that in Grop L（P＜0.05）; the patients in Group N was no longer fear of cystoscopy. Part Ⅲ:There were no significant differences in the physical characteristics of patientsbetween the two groups （P＜0.05）; compared with group L, the plasmalidocaine concentration was significantly lower in group N, while Tpeak,Cmax and AUC were significantly lower, CL and Vd were significantly hihgerin group N than that in group L（P＜0.05）.Conclusions: Lidocaine gel with pH7.20is stable; alkalize lidocaine gelto pH7.20increased the topical anesthetic potential of gel; alkalization of thegel reduce the distribution of lidocaine in plasma, and thus reduced itstoxicity.