目的通过尼扎替丁的大鼠体内、外实验,观察尼扎替丁对大鼠CYP1A2亚型的影响。方法通过HPLC法测定全血中咖啡因的代谢率,观测尼扎替丁对大鼠CYP1A2活性的影响;通过W estern b lot法测定尼扎替丁对大鼠肝微粒体CYP1A2蛋白表达的调控;通过H...目的通过尼扎替丁的大鼠体内、外实验,观察尼扎替丁对大鼠CYP1A2亚型的影响。方法通过HPLC法测定全血中咖啡因的代谢率,观测尼扎替丁对大鼠CYP1A2活性的影响;通过W estern b lot法测定尼扎替丁对大鼠肝微粒体CYP1A2蛋白表达的调控;通过HPLC法测定肝微粒体重组系统对乙酰氨基酚的含量,确定尼扎替丁对大鼠肝微粒体CYP1A2亚型的作用。结果实验组中给予大鼠不同浓度的尼扎替丁(14、27、54 mg.kg-1),其咖啡因代谢率为29.6%±12.5%、32.4%±13.4%、37.5%±15.0%,对照组为26.9%±11.9%,各剂量组及对照组间差异均无显著性(P>0.05);实验各剂量组与对照组的CYP1A2蛋白表达差异无显著性;肝微粒体体外重组系统中,实验组各浓度尼扎替丁对CYP1A2没有抑制作用,CYP1A2的活性>100%;对照组α-萘黄酮有明显的抑制作用,IC50=0.0306μmol.L-1。结论体内、外实验结果均表明尼扎替丁对大鼠CYP1A2没有抑制作用。展开更多
AIM To examine whether nizatidine stimulates duodenal HCO_3^- secretion in rats by inhibiting AChE activity. METHODS Under pentobarbital anesthesia,a proximal duodenal loop was perfused with saline,and the HCO_3 secre...AIM To examine whether nizatidine stimulates duodenal HCO_3^- secretion in rats by inhibiting AChE activity. METHODS Under pentobarbital anesthesia,a proximal duodenal loop was perfused with saline,and the HCO_3 secretion was measured at pH 7.0 using a pH-stat method and by adding 10mM HCI.Nizatidine,neostigmine,carbachol or famotidine was administered i.v.as a single injection. RESULTS Intravenous administration of nizatidine(3-30 mg/kg)dose-dependently increased duodenal HCO_3^- secretion,and the effect at 10mg/kg was equivalent to that obtained by carbachol at 0.01 mg/kg.This nizatidine action was observed at the same dose range that inhibited acid secretion and enhanced gastric motility,mimicked by i.v.injection of neostigmine(0.03 mg/kg),and significantly attenuated by bilateral vagotomy and prior s.c. administration of atropine but not by indomethacin,a cyclooxygenase inhibitor,or N^G-nitro-L-arginine methyl ester,a NO synthase inhibitor.The HCO_3^- secretory response to acetylcholine(0.001 mg/kg)was significantly potentiated by the concurrent administration of nizatidine(3mg/kg,i.v.).The IC_(50)of nizatidine for AChE of rat erythrocytes was 1.4×10^(-6)M,about 12 times higher than that of neostigmine.Neither famotidine(>10^(-3)M, 30mg/kg,i.v.)nor cisapride(> 10^(-3)M, 3mg/kg,i.v.)had any influence on AChE activity or duodenal HCO_3^- secretion.Duodenal damage induced by acid perfusion(100 mM HCI for 4 h)in the presence of indomethacin was significantly prevented by nizatidine and neostigmine,at the doses that increased the HCO_3^- secretion. CONCLUSION Nizatidine stimulates duodenal HCO_3^- secretion,in both vagal-dependent and atropine-sensitive manners,and the action is associated with the anti-AChE activity of this agent.展开更多
This research article describes stability indicating fast liquid chromatographic method for determination of chromatographic purity and assay of Nizatidine as a alternate for two different methods for chromatographic ...This research article describes stability indicating fast liquid chromatographic method for determination of chromatographic purity and assay of Nizatidine as a alternate for two different methods for chromatographic purity and assay as given in USP Monograph and Ph.Eur Monograph. Proposed method is developed on Waters symmetry RP18 (50 × 4.6 mm), 3.5 μm stationary phase using gradient elution with combination of Ammonium acetate Diethyl amine buffer, Methanol and Tetrahydrofuran as mobile phase. Favorable results are obtained under developed conditions, which guarantee good separation of studied components. Whereas, data obtained from method validation confirm specificity, high sensitivity, linearity in a range of studied concentrations, repeatability and good accuracy of this method. Considerable degradation observed in oxidation stress condition was detected by this method. Eight impurities are studied among which impurity-5 is found major degradant. The stress samples are assayed against a qualified standard and the mass balance is found close to 99.2%. The developed method can be used for routine samples as well as stability studies.展开更多
AIM: To elucidate the effect of saliva stimulation by nizatidine on oral symptoms of primary biliary cirrhosis (PBC) by administering it to PBC cases. METHODS: From among 73 cases that had been definitively diagnosed ...AIM: To elucidate the effect of saliva stimulation by nizatidine on oral symptoms of primary biliary cirrhosis (PBC) by administering it to PBC cases. METHODS: From among 73 cases that had been definitively diagnosed as PBC at our hospital by February 2010, we selected 27 cases of PBC, 4 males and 23 females, as subjects. We obtained subjects' consent after giving them a full explanation of the administration of nizatidine. Nizatidine 150 mg was administered internally twice daily, after morning and evening meals. To observe changes in the quantity of saliva secreted, chewing gum tests were carried out four times: before the initial dose, and after 6 mo, 12 mo and 24 mo of administration. For subjective dry mouth symptoms, a visual analog scale (VAS) method was used to assess their feelings of oral dryness and eating difficulty, five times: before the initial dose, and after 1, 6, 12 and 24 mo of administration in 8 cases. The nutritional condition and the hepatic functional reserve were compared between before and after the nizatidine treatment.RESULTS: The result of a chewing gum test on the subjects before the administration of nizatidine showed that 50% produced less than 10 mL of saliva, i.e. , the standard under which cases are considered to have hyposalivation. The results of these tests showed that the quantity of saliva secreted was 10.5 ± 6.8 mL before administration of nizatidine, 10.9 ± 6.0 mL after 6 mo, 10.6 ± 4.9 mL after 12 mo, and 11.8 ± 6.8 mL after 24 mo administration. Thus, there was a slowly increasing trend in the quantity of saliva in the whole group. The percentage of subjects with saliva production above 10 mL was 45.8% after 6 mo administration of nizatidine, that is, only a slight change from before its administration, but it was 64.3% after 12 mo, that is, a significant increase. The saliva secretion by subject patients was examined before the beginning of administration of nizatidine, 12 mo later, and 24 mo later, and Fisher's combined probability test was used to examine the res展开更多
A validated simple and sensitive high performance liquid chromatographic（HPLC） method for the quantitative determination of nizatidine（NIZ） in human plasma and urine is reported.Reverse phase chromatographic separ...A validated simple and sensitive high performance liquid chromatographic（HPLC） method for the quantitative determination of nizatidine（NIZ） in human plasma and urine is reported.Reverse phase chromatographic separation of NIZ and salicylic acid（internal standard） was achieved on Diamonsil C_（18） column,using acetonitrile-0.05 mol/L K_2HPO_4-triethylamine （17：83：1,v/v/v,pH 6.5） as the mobile phase.Flow rate was 0.9 mL/min and the ultraviolet detector was set at a wavelength of 320 nm.The assay was linear over the range of 0.0117-6 mg/mL for plasma samples and 0.029-50 ug/mL for urine samples. The limit of quantification was 0.0117μg/mL.The intra- and inter-day RSD values were lower than 5.12%and 8.03%,respectively, in plasma,and 6.2%and 6.9%,respectively,in urine.A single dose of 100 mg NIZ and multiple doses of 100 mg NIZ were administered to 10 healthy volunteers through intravenous infusions.The multiple dose regimens were administered every 8 h for 6 consecutive days.The pharmacokinetic parameters were obtained as following：for single-dose,Cmax（2.7±0.6）μg/mL, t1/2（1.4±0.4） h,AUC0-12h（2.45±0.33）μg·h/mL,AUC0-∞（2.46±0.33）μg·h/mL,and the accumulated urine excretion rate in 12 h was 61.2%±9.46%;for multiple doses,Cmax（2.9±0.8）μg/mL,t1/2（l.3±0.2） h,AUC0-12h（2.56±0.52）μg·h/mL,AUC0-∞ （2.56±0.52）μg·h/mL,and the accumulated urine excretion rate in 12 h was 51.3%±9.42%.The statistical analysis of the pharmacokinetic parameters in males and females after single-dose and multiple-dose intravenous infusion of NIZ showed no differences.No drug accumulation after multiple-dose intravenous infusion of 100 mg NIZ was observed.The validated HPLC method was suitable for the pharmacokinetic study of NIZ.展开更多
文摘目的通过尼扎替丁的大鼠体内、外实验,观察尼扎替丁对大鼠CYP1A2亚型的影响。方法通过HPLC法测定全血中咖啡因的代谢率,观测尼扎替丁对大鼠CYP1A2活性的影响;通过W estern b lot法测定尼扎替丁对大鼠肝微粒体CYP1A2蛋白表达的调控;通过HPLC法测定肝微粒体重组系统对乙酰氨基酚的含量,确定尼扎替丁对大鼠肝微粒体CYP1A2亚型的作用。结果实验组中给予大鼠不同浓度的尼扎替丁(14、27、54 mg.kg-1),其咖啡因代谢率为29.6%±12.5%、32.4%±13.4%、37.5%±15.0%,对照组为26.9%±11.9%,各剂量组及对照组间差异均无显著性(P>0.05);实验各剂量组与对照组的CYP1A2蛋白表达差异无显著性;肝微粒体体外重组系统中,实验组各浓度尼扎替丁对CYP1A2没有抑制作用,CYP1A2的活性>100%;对照组α-萘黄酮有明显的抑制作用,IC50=0.0306μmol.L-1。结论体内、外实验结果均表明尼扎替丁对大鼠CYP1A2没有抑制作用。
文摘AIM To examine whether nizatidine stimulates duodenal HCO_3^- secretion in rats by inhibiting AChE activity. METHODS Under pentobarbital anesthesia,a proximal duodenal loop was perfused with saline,and the HCO_3 secretion was measured at pH 7.0 using a pH-stat method and by adding 10mM HCI.Nizatidine,neostigmine,carbachol or famotidine was administered i.v.as a single injection. RESULTS Intravenous administration of nizatidine(3-30 mg/kg)dose-dependently increased duodenal HCO_3^- secretion,and the effect at 10mg/kg was equivalent to that obtained by carbachol at 0.01 mg/kg.This nizatidine action was observed at the same dose range that inhibited acid secretion and enhanced gastric motility,mimicked by i.v.injection of neostigmine(0.03 mg/kg),and significantly attenuated by bilateral vagotomy and prior s.c. administration of atropine but not by indomethacin,a cyclooxygenase inhibitor,or N^G-nitro-L-arginine methyl ester,a NO synthase inhibitor.The HCO_3^- secretory response to acetylcholine(0.001 mg/kg)was significantly potentiated by the concurrent administration of nizatidine(3mg/kg,i.v.).The IC_(50)of nizatidine for AChE of rat erythrocytes was 1.4×10^(-6)M,about 12 times higher than that of neostigmine.Neither famotidine(>10^(-3)M, 30mg/kg,i.v.)nor cisapride(> 10^(-3)M, 3mg/kg,i.v.)had any influence on AChE activity or duodenal HCO_3^- secretion.Duodenal damage induced by acid perfusion(100 mM HCI for 4 h)in the presence of indomethacin was significantly prevented by nizatidine and neostigmine,at the doses that increased the HCO_3^- secretion. CONCLUSION Nizatidine stimulates duodenal HCO_3^- secretion,in both vagal-dependent and atropine-sensitive manners,and the action is associated with the anti-AChE activity of this agent.
文摘This research article describes stability indicating fast liquid chromatographic method for determination of chromatographic purity and assay of Nizatidine as a alternate for two different methods for chromatographic purity and assay as given in USP Monograph and Ph.Eur Monograph. Proposed method is developed on Waters symmetry RP18 (50 × 4.6 mm), 3.5 μm stationary phase using gradient elution with combination of Ammonium acetate Diethyl amine buffer, Methanol and Tetrahydrofuran as mobile phase. Favorable results are obtained under developed conditions, which guarantee good separation of studied components. Whereas, data obtained from method validation confirm specificity, high sensitivity, linearity in a range of studied concentrations, repeatability and good accuracy of this method. Considerable degradation observed in oxidation stress condition was detected by this method. Eight impurities are studied among which impurity-5 is found major degradant. The stress samples are assayed against a qualified standard and the mass balance is found close to 99.2%. The developed method can be used for routine samples as well as stability studies.
文摘AIM: To elucidate the effect of saliva stimulation by nizatidine on oral symptoms of primary biliary cirrhosis (PBC) by administering it to PBC cases. METHODS: From among 73 cases that had been definitively diagnosed as PBC at our hospital by February 2010, we selected 27 cases of PBC, 4 males and 23 females, as subjects. We obtained subjects' consent after giving them a full explanation of the administration of nizatidine. Nizatidine 150 mg was administered internally twice daily, after morning and evening meals. To observe changes in the quantity of saliva secreted, chewing gum tests were carried out four times: before the initial dose, and after 6 mo, 12 mo and 24 mo of administration. For subjective dry mouth symptoms, a visual analog scale (VAS) method was used to assess their feelings of oral dryness and eating difficulty, five times: before the initial dose, and after 1, 6, 12 and 24 mo of administration in 8 cases. The nutritional condition and the hepatic functional reserve were compared between before and after the nizatidine treatment.RESULTS: The result of a chewing gum test on the subjects before the administration of nizatidine showed that 50% produced less than 10 mL of saliva, i.e. , the standard under which cases are considered to have hyposalivation. The results of these tests showed that the quantity of saliva secreted was 10.5 ± 6.8 mL before administration of nizatidine, 10.9 ± 6.0 mL after 6 mo, 10.6 ± 4.9 mL after 12 mo, and 11.8 ± 6.8 mL after 24 mo administration. Thus, there was a slowly increasing trend in the quantity of saliva in the whole group. The percentage of subjects with saliva production above 10 mL was 45.8% after 6 mo administration of nizatidine, that is, only a slight change from before its administration, but it was 64.3% after 12 mo, that is, a significant increase. The saliva secretion by subject patients was examined before the beginning of administration of nizatidine, 12 mo later, and 24 mo later, and Fisher's combined probability test was used to examine the res
文摘A validated simple and sensitive high performance liquid chromatographic（HPLC） method for the quantitative determination of nizatidine（NIZ） in human plasma and urine is reported.Reverse phase chromatographic separation of NIZ and salicylic acid（internal standard） was achieved on Diamonsil C_（18） column,using acetonitrile-0.05 mol/L K_2HPO_4-triethylamine （17：83：1,v/v/v,pH 6.5） as the mobile phase.Flow rate was 0.9 mL/min and the ultraviolet detector was set at a wavelength of 320 nm.The assay was linear over the range of 0.0117-6 mg/mL for plasma samples and 0.029-50 ug/mL for urine samples. The limit of quantification was 0.0117μg/mL.The intra- and inter-day RSD values were lower than 5.12%and 8.03%,respectively, in plasma,and 6.2%and 6.9%,respectively,in urine.A single dose of 100 mg NIZ and multiple doses of 100 mg NIZ were administered to 10 healthy volunteers through intravenous infusions.The multiple dose regimens were administered every 8 h for 6 consecutive days.The pharmacokinetic parameters were obtained as following：for single-dose,Cmax（2.7±0.6）μg/mL, t1/2（1.4±0.4） h,AUC0-12h（2.45±0.33）μg·h/mL,AUC0-∞（2.46±0.33）μg·h/mL,and the accumulated urine excretion rate in 12 h was 61.2%±9.46%;for multiple doses,Cmax（2.9±0.8）μg/mL,t1/2（l.3±0.2） h,AUC0-12h（2.56±0.52）μg·h/mL,AUC0-∞ （2.56±0.52）μg·h/mL,and the accumulated urine excretion rate in 12 h was 51.3%±9.42%.The statistical analysis of the pharmacokinetic parameters in males and females after single-dose and multiple-dose intravenous infusion of NIZ showed no differences.No drug accumulation after multiple-dose intravenous infusion of 100 mg NIZ was observed.The validated HPLC method was suitable for the pharmacokinetic study of NIZ.
