This work aimed to set up a high performance liquid chromatography (HPLC) method to determine the concentration of lansoprazole in human plasma and study the pharmacokinetic characters of lansoprazole in Chinese healthy volunteers after intravenous (IV) infusion. In accordance with double 3 x 3 Latin square design with self-crossover design, 12 volunteers were randomly divided into six groups, with half males and half females. The volunteers were administered with single dose of 15, 30, 60 mg of lansoprazole by IV infusion at a constant speed respectively, to study the clinical pharmacokinetics of lansoprazole. The linear range of lansoprazole in human plasma was 0.020-4.970 microg/ml (r = 0.9999); The intra-day and inter-day RSD were less than 10%. After receiving single doses of 15, 30 and 60 mg of lansoprazole, t(1/2) were (1.663 +/- 0.405) h, (1.541 +/- 0.339)h and (1.747 +/- 0.156) h; Cmax were (1.065 +/- 0.094) microg/ml, (2.104 +/- 0.312) microg/ml and (3.786 +/- 0.356) microg/ml; AUC(0-infinity) were (2.376 +/- 0. 432) microg x h/ ml, (4.722 +/- 0.753) microg x h/ml and (10.495 +/- 2.129) microg x h/ml respectively. The improved HPLC method is simple, rapid and reproducible. It could be used for determination of the concentration of lansoprazole in human plasma. The pharmacokinetics of lansoprazole for injection was found to fit the linear dynamics in vivo within the dose range of 15 to 60 mg. In addition, the results suggested that gender had no statistic significant effect on the pharmacokinetic process of lansoprazole after IV infusion of single dose.
2-Pyridinylmethylsulfinylbenzimidazoles ; administration & dosage ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; methods ; Female ; Humans ; Infusions, Intravenous ; Lansoprazole ; Male ; Proton Pump Inhibitors

OBJECTIVE: To observe the clinical efficacy of sequential therapy with pantoprazole in patients with gastro esophageal reflux disease (GERD). METHODS: A total of 80 patients with GERD were double-blindedly randomized into 2 groups: 40 patients received sequential therapy with pantoprazole 40 mg injection, twice daily for 2 weeks, and then pantoprazole 40 mg oral administration,twice daily for 2 weeks; the other 40 patients received pantoprazole 40 mg oral administration alone,twice daily for 4 weeks. Doctors and patients recorded the severity and frequency of heartburn before and during the treatment. The curative effects of the 2 groups were compared. RESULTS: The total effective rate in the sequential therapy group was higher than that of the oral administration group(95.0% vs 77.5%, P<0.05). CONCLUSION Pantoprazole sequential therapy is effective for GERD.
2-Pyridinylmethylsulfinylbenzimidazoles ; administration & dosage ; therapeutic use ; Double-Blind Method ; Drug Administration Schedule ; Female ; Gastroesophageal Reflux ; drug therapy ; Humans ; Male ; Middle Aged ; Pantoprazole ; Proton Pump Inhibitors ; administration & dosage ; therapeutic use

This study is to investigate the effect of high altitude hypoxia on the activity and protein expression of CYP2C9 and CYP2C19. Rats from plain (P) and rats with acute middle altitude hypoxia (AMH), chronic middle altitude hypoxia (CMH), acute high altitude hypoxia (AHH) and chronic high altitude hypoxia (CHH) were administered orally phenytoin sodium (PHT) and omeprazole (OMZ) to evaluate the activity of CYP2C9 and CYP2C19, separately. The serum concentrations of PHT and metabolite 4'-hydroxyphenytoin (HPPH) at 12 h after treatment and the serum concentrations of OMZ and metabolite 5-hydroxy omeprazole (5-OHOMZ) at 3 h after treatment were determined by RP-HPLC. The activity of CYP2C9 and CYP2C19 was evaluated by the ratio of HPPH to PHT and the ratio of 5-OHOMZ to OMZ, respectively. The protein expressions of CYP2C9 and CYP2C19 were determined by ELISA method. The activities of CYP2C9 (HPPH/PHT) in P, AMH, CMH, AHH and CHH were 0.67 +/- 0.31, 0.75 +/- 0.29, 0.76 +/- 0.23, 0.79 +/- 0.31 and 0.75 +/- 0.18, respectively, and the activities of CYP2C19 (5-OHOMZ/OMZ) in P, AMH, CMH, AHH and CHH were 0.17 +/- 0.06, 0.20 +/- 0.10, 0.11 +/- 0.05, 0.37 +/- 0.13 and 0.19 +/- 0.05, respectively. The protein expressions of CYP2C9 in P, AMH, CMH, AHH and CHH were 4.20 +/- 1.27, 3.95 +/- 0.81, 3.93 +/- 1.11, 4.32 +/- 1.03 and 4.12 +/- 0.86 ng x g(-1), respectively, and the protein expressions of CYP2C19 in P, AMH, CMH, AHH and CHH were 3.91 +/- 1.82, 3.63 +/- 2.07, 2.55 +/- 0.85, 4.78 +/- 2.37 and 3.51 +/- 1.03 ng x g(-1), respectively. The activities and protein expressions of CYP2C9 in AMH, CMH, AHH and CHH were not significantly different with those of P. The protein expressions of CYP2C19 in AMH, CMH, AHH and CHH were not significantly different with those of P, but the activity of CYP2C19 in AHH was significantly higher than that of P. This study found significant changes in the activity of CYP2C19 under the special environment of acute high altitude hypoxia.
2-Pyridinylmethylsulfinylbenzimidazoles ; blood ; Administration, Oral ; Altitude ; Animals ; Cytochrome P-450 Enzyme System ; metabolism ; Enzyme Activation ; Female ; Hypoxia ; metabolism ; Male ; Omeprazole ; administration & dosage ; blood ; pharmacokinetics ; Phenytoin ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

This study is to prepare the pantoprazole sodium enteric-coated tablet which is compacted by pellets. The enteric-coated pantoprazole sodium pellets were prepared by fluid bed coating technology. The pantoprazole sodium enteric-coated tablets were prepared by direct compression of the enteric-coated pellets and suitable excipients. In vitro dissolution method and scanning electron microscope method were used for the observation of the drug release behavior before and after compression of the pellets. The optimized formulation is: the coating level is 55%, the plasticizer content is 20%, the ratio of Eudragit L30D-55/NE30D is 8 : 2, enteric-coated pellets/excipients (MCC/PPVP/PEG 6000 = 2 : 1 : 1) is 5 : 5, the enteric-coated tablets release in artificial gastric fluid in 2 h is less than 10%, while in artificial intestinal fluid in 1 h is more than 85%. The release behavior of pantoprazole sodium enteric-coated pellets-type tablet is quite well. And it may be used in industrial production.
2-Pyridinylmethylsulfinylbenzimidazoles ; administration & dosage ; chemistry ; Chromatography, High Pressure Liquid ; methods ; Drug Carriers ; Drug Compounding ; methods ; Excipients ; Microscopy, Electron, Scanning ; Plasticizers ; chemistry ; Polyethylene Glycols ; chemistry ; Polymethacrylic Acids ; chemistry ; Proton Pump Inhibitors ; administration & dosage ; chemistry ; Solubility ; Tablets, Enteric-Coated ; chemistry ; Technology, Pharmaceutical

BACKROUND/AIMS: Bismuth-based quadruple therapy for second-line eradication treatment achieves the eradication rate ranging from 70% to 81% due to antimicrobial resistance and poor compliance. The aim of this study was to compare the eradication rate of levofloxacin-based triple therapy with that of bismuth-based quadruple therapy in second-line Helicobacter pylori (H. pylori) eradication therapy. METHODS: Seventy-six outpatients with persistent H. pylori infection after first-line triple therapy were enrolled in this prospective randomized trial. The subjects were randomized to receive levofloxacin 300 mg, amoxicillin 1 g, and pantoprazole 20 mg, given twice daily for 7 days (LAP group), or metronidazole 500 mg twice, tetracycline 500 mg four times, and pantoprazole 20 mg twice, bismuth subcitrate 600 mg twice daily for 7 days (MTPB group). Eradication was confirmed with 13C-urea breath test or rapid urease test 4 weeks after the cessation of therapy. RESULTS: Among Seventy-six patients initially included, eleven were lost during follow-up. The eradication rates, expressed as intention to treat (ITT) and per protocol (PP) analyses, were 51.6% and 53.3% in the LAP group, and 48.9% and 62.9% in the MTPB group, respectively. There was no significant difference in H. pylori eradication rates between the two groups (p=0.815 by ITT, p=0.437 by PP). LAP regimen was better tolerated than MTPB regimen with lower incidence of side effects (10.0% versus 31.4%, p=0.03). CONCLUSIONS: H. pylori eradication rates of levofloxacin-based triple therapy and bismuth-based quadruple therapy were not significantly different in second-line H. pylori eradication therapy, and low incidence of side effects was observed in levofloxacin-based triple therapy.
2-Pyridinylmethylsulfinylbenzimidazoles/administration & dosage ; Adult ; Antacids/administration & dosage ; Anti-Bacterial Agents/*administration & dosage ; Anti-Ulcer Agents/administration & dosage ; Data Interpretation, Statistical ; Drug Therapy, Combination ; Female ; Helicobacter Infections/*drug therapy/microbiology ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Ofloxacin/*administration & dosage ; Organometallic Compounds/administration & dosage ; Time Factors ; Treatment Outcome

AIMTo study the chiral inversion of dextropantoprazole in human.

METHODSThree healthy Chinese male volunteers after an oral dose of 40 mg dextropantoprazole. An HPLC method was developed and used to determine the total plasma concentrations of each enantiomer. The ratios of the enantiomers in plasma samples were measured on a Chiral-AGP column. The plasma concentration of each enantiomer was then calculated using the ratios of enantiomers and total concentrations of the two enantiomers previously measured.

RESULTSThe AUC0-t of levopantoprazole was only 1.5% of the total AUC0-t of enantiomers.

CONCLUSIONThe chiral inversion from dextropantoprazole to levopantoprazole does not occur in the three healthy Chinese male volunteers after an oral dose of 40 mg dextropantoprazol.

2-Pyridinylmethylsulfinylbenzimidazoles ; Administration, Oral ; Adult ; Anti-Ulcer Agents ; blood ; chemistry ; pharmacokinetics ; Area Under Curve ; Benzimidazoles ; blood ; chemistry ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Humans ; Male ; Omeprazole ; analogs & derivatives ; blood ; chemistry ; pharmacokinetics ; Stereoisomerism ; Sulfoxides ; blood ; chemistry ; pharmacokinetics

OBJECTIVE: To evaluate the efficacy and safety of 4 kinds of triple strategy of Helicobacter pylori (Hp) eradication. METHODS: A total of 307 patients who suffered from Hp infection, confirmed by rapid urease test (RUT) and 14C-urea breath test (UBT),were randomly divided into 4 groups. Each group had 80, 76, 77, and 74 patients respectively. Group A was treated with rabeprazole, clarithromycin, and furazolidone (RCF); Group B with ranitidine bismuth citrate, clarithromycin, and furazolidone (BCF); Group C with rabeprazole, amoxicillin, and furazolidone (RAF); while Group D with ranitidine bismuth citrate, amoxicillin, and furazolidone (BAF). Hp was detected by RUT and UBT at 4 weeks after later treatment. RESULTS: Hp eradication rates of group A,B,C, and D were 90.0%,67.1%,62.3%,and 45.9%,respectively. The difference between Group A and Group B, Group A and Group C was significant (P<0.05). Eradication rate of Group B and C was higher than that of Group D (P<0.05). There was no statistical difference between the eradication rate of Group B and C, and among the side effects of the 4 groups. CONCLUSION The strategy of RCF was the best among the 4 triple strategy of Hp eradication, which can be used clinically.
2-Pyridinylmethylsulfinylbenzimidazoles ; administration & dosage ; Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; administration & dosage ; Anti-Ulcer Agents ; administration & dosage ; Clarithromycin ; administration & dosage ; Drug Therapy, Combination ; Duodenal Ulcer ; microbiology ; Female ; Furazolidone ; administration & dosage ; Helicobacter Infections ; drug therapy ; Helicobacter pylori ; Humans ; Male ; Middle Aged ; Rabeprazole ; Stomach Ulcer ; microbiology ; Young Adult

BACKGROUNE/AIMS: Esophageal variceal ligation (EVL) is the most preferable method for controling variceal bleeding. However, EVL is associated with complications such as hemorrhage, chest pain, dysphagia, and odynophagia due to post-EVL ulcers in the esophageal mucosa. The aim of this study was to assess the effect of proton pump inhibitor (PPI), pantoprazole on the healing of post-EVL ulcers. METHODS: Forty seven patients were randomly allocated into PPI group and control group. Patients in PPI group received 40 mg of pantoprazole intravenously for 3 days after EVL, then 40 mg of oral pantoprazole for 11 days consecutively. Control patients received intravenous and oral placebo. Endoscopic examinations were performed twice at 7+/-2 days and 14+/-2 days after EVL respectively. Clinical outcomes include the size of ulcers, symptoms reported by patients; chest pain, dysphagia, and odynophagia. RESULTS: Forty seven patients completed the 7 days protocol (PPI/control; 25/22), and twenty six patients completed the 14 days protocol (PPI/control; 16/10). Post-EVL ulcers in PPI group were significantly smaller than those in control group (7 days; 98.7 mm2/119.4 mm2, 14 days; 32.3 mm2/43.8 mm2, p<0.01). No difference was observed between two the groups with respect to summations of symptom scores (p>0.05). Nineteen patients (PPI/control; 9/10) did not complete the 14 days protocol due to patients' refusal and adverse outcomes, such as hepatic failure and sepsis with bleeding from post-EVL ulcer occurred in two patients of control group. CONCLUSIONS: PPI treatment following EVL may be effective in healing post-EVL ulcer.
2-Pyridinylmethylsulfinylbenzimidazoles/administration & dosage/*therapeutic use ; Anti-Ulcer Agents/administration & dosage/*therapeutic use ; Esophageal and Gastric Varices/complications/*surgery ; Esophagoscopy ; Female ; Gastrointestinal Hemorrhage/prevention & control ; Humans ; Ligation ; Male ; Middle Aged ; Proton Pump Inhibitors/administration & dosage/*therapeutic use ; Regression Analysis ; Sickness Impact Profile ; Ulcer/*drug therapy/etiology

BACKGROUND/AIMS: Genetic polymorphism of cytochrome P450 CYP2C19 influences the efficacy of proton pump inhibitor (PPI) in Helicobacter pylori (H. pylori) eradication therapy. We investigated the difference in the cure rates of H. pylori infection by triple (rabeprazole plus amoxacillin and clarithromycin) therapy in relation to CYP2C19 genotype status. METHODS: One hundred and sixteen H. pylori infected patients with gastric ulcer and duodenal ulcer completed the triple therapy with 10 mg of rabeprazole b.i.d., 1,000 mg amoxacillin b.i.d. and 500 mg of clarithromycin b.i.d. for one week. The genotype of CYP2C19 was determined by a PCR-restriction fragment length polymorphism method. RESULTS: According to the univariate analysis, heterozygous extensive metabolizers (hetero EMs) and poor metabolizers (PMs) showed the highest (87.0%) and the lowest (80.0%) eradication rates, respectively. The difference in the therapeutic efficacy of rabeprazole among the different CYP2C19 genotypes was insignificant. With regard to gender, age and smoking history in relation to eradication rate, a statistical significance was noted only with age with odds ratio of 1.063 and p-value of 0.0202. CONCLUSIONS: In the eradication therapy of H. pylori, no statistically significant difference in therapeutic efficacy of rabeprazole was found among different CYP2C19 genotypes.
2-Pyridinylmethylsulfinylbenzimidazoles ; Adult ; Aged ; Amoxicillin/administration & dosage ; Anti-Bacterial Agents/administration & dosage ; Anti-Ulcer Agents/*administration & dosage ; Aryl Hydrocarbon Hydroxylases/*genetics ; Benzimidazoles/*administration & dosage ; Clarithromycin/administration & dosage ; Drug Therapy, Combination ; Duodenal Ulcer/drug therapy/*genetics/microbiology ; Female ; Genotype ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Mixed Function Oxygenases/*genetics ; Omeprazole/analogs & derivatives ; Proton Pumps/*antagonists & inhibitors ; Stomach Ulcer/drug therapy/*genetics/microbiology

BACKGROUND/AIMS: Conflicting results have been reported whether patients with non-ulcer dyspepsia (NUD) respond differently to Helicobacter pylori (H. pylori) eradication treatment compared with patients with peptic ulcer diseases (PUD). The aim of this study was to evaluate any difference in H. pylori eradication rates between patients with NUD and PUD according to each proton pump inhibitor (PPI). METHODS: From September, 2004 to April, 2007, we retrospectively reviewed 2,297 patients with NUD (1,050 patients) or PUD (1,247 patients) infected with H. pylori. All patients received a standard 1 week triple therapy comprising of one of the five PPIs (pantoprazole, esomeprazole, omeprazole, lansoprazole, rabeprazole), clarithromycin and amoxicillin. The follow-up H. pylori test was performed 4 weeks after the completion of therapy. RESULTS: There was no significant difference in the eradication rates between the two groups. In comparison of eradication rates according to PPI, omeprazole- based triple therapy group showed higher eradication rate than other groups in patients with NUD, but not in patients with PUD. CONCLUSIONS: This study failed to show any difference in H. pylori eradication rate between patients with NUD and PUD. There is no convincing evidence that the eradication rate may be affected by different PPI.
2-Pyridinylmethylsulfinylbenzimidazoles/therapeutic use ; Adult ; Amoxicillin/administration & dosage ; Anti-Bacterial Agents/administration & dosage ; Anti-Ulcer Agents/administration & dosage ; Clarithromycin/administration & dosage ; Data Interpretation, Statistical ; Drug Therapy, Combination ; Dyspepsia/*drug therapy/etiology/microbiology ; Enzyme Inhibitors/therapeutic use ; Female ; Helicobacter Infections/complications/*drug therapy/microbiology ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Omeprazole/analogs & derivatives/therapeutic use ; Peptic Ulcer/*drug therapy/etiology/microbiology ; Proton Pump Inhibitors/therapeutic use