To investigate the efficacy of bismuth containing quadruple therapies on Helicobacter pylori (Hp) eradication in patients with history of antibiotic treatment. 
 Methods: Hp infected patients (n=327) were allocated into 3 groups. Group A (n=52), patients had no antibiotic history and they took medicine of proton pump inhibitors (PPI) and livzon triple (clarithromycin, tinidazole, and bismuth); group B (n=80), patients had the antibiotic history except for amoxicillin and clarithromycin, and they were treated with PPI, amoxicillin, clarithromycin, and bismuth; group C (n=195), patients suffered failures of Hp therapy or with history of antibiotic abuse, and they were treated with PPI, doxycycline, furazolidone, and bismuth.
 Results: Both the intention-to-treat (ITT) analysis (group A 63.5%, group B 76.2%, group C 82.6%, P<0.05) and the pre-protocol (PP) analysis (group A 76.7%, group B 92.4%, group C 96.4%, P<0.05) showed significant difference among the 3 groups, revealing higher elimination in group B and C. The side-effects (20.2%) were mild and tolerable (group A, 28.0%; group B, 10.7%; group C, 22.0%).
 Conclusion: Proton pump inhibitors together with the livzon triple regimen have a low rate of Hp eradication and a higher incidence of adverse reactions. The quadruple therapy containing clarithromycin and metronidazole drugs can achieve the satisfactory outcomes based on patient's antibiotic history. For patients with multiple antibiotics, the quadruple therapy containing furazolidone and doxycycline may achieve the satisfactory outcomes, but the adverse resction would be relatively higher.
Amoxicillin ; therapeutic use ; Anti-Bacterial Agents ; therapeutic use ; Bismuth ; therapeutic use ; Clarithromycin ; therapeutic use ; Drug Therapy, Combination ; methods ; Furazolidone ; therapeutic use ; Helicobacter Infections ; drug therapy ; Helicobacter pylori ; Humans ; Metronidazole ; therapeutic use ; Proton Pump Inhibitors ; therapeutic use ; Tinidazole ; therapeutic use ; Treatment Outcome

BACKGROUNDHelicobacter pylori (H. pylori) frequently colonizes the stomach. Gastroesophageal reflux disease (GERD) is a common and costly disease. But the relationship of H. pylori and GERD is still unclear. This study aimed to explore the effect of H. pylori and its eradication on reflux esophagitis therapy.

METHODSPatients diagnosed with reflux esophagitis by endoscopy were enrolled; based on rapid urease test and Warth-Starry stain, they were divided into H. pylori positive and negative groups. H. pylori positive patients were randomly given H. pylori eradication treatment for 10 days, then esomeprazole 20 mg bid for 46 days. The other patients received esomeprazole 20 mg bid therapy for 8 weeks. After treatment, three patient groups were obtained: H. pylori positive eradicated, H. pylori positive uneradicated, and H. pylori negative. Before and after therapy, reflux symptoms were scored and compared. Healing rates were compared among groups. The χ2 test and t-test were used, respectively, for enumeration and measurement data.

RESULTSThere were 176 H. pylori positive (with 92 eradication cases) and 180 negative cases. Healing rates in the H. pylori positive eradicated and H. pylori positive uneradicated groups reached 80.4% and 79.8% (P = 0.911), with reflux symptom scores of 0.22 and 0.14 (P = 0.588). Healing rates of esophagitis in the H. pylori positive uneradicated and H. pylori negative groups were, respectively, 79.8% and 82.2% (P = 0.848); reflux symptom scores were 0.14 and 0.21 (P = 0.546).

CONCLUSIONSBased on esomeprazole therapy, H. pylori infection and eradication have no significant effect on reflux esophagitis therapy.

Adolescent ; Adult ; Aged ; Amoxicillin ; therapeutic use ; Esomeprazole ; therapeutic use ; Esophagitis, Peptic ; drug therapy ; etiology ; microbiology ; Female ; Gastroesophageal Reflux ; drug therapy ; etiology ; microbiology ; Helicobacter Infections ; complications ; drug therapy ; Helicobacter pylori ; drug effects ; pathogenicity ; Humans ; Male ; Middle Aged ; Tinidazole ; therapeutic use ; Young Adult

Proton pump inhibitor (PPI)-based triple therapy consisting of PPI, amoxicillin, and clarithromycin, is the recommended first-line treatment for Helicobacter pylori infection. However, the eradication rate of triple therapy has declined over the past few decades. We analyzed the eradication rate and adverse events of triple therapy to evaluate current practices in Korea. A comprehensive literature search was performed up to August 2013 of 104 relevant studies comprising 42,124 patients. The overall eradication rate was 74.6% (95% confidence interval [CI], 72.1%-77.2%) by intention-to-treat analysis and 82.0% (95% CI, 80.8%-83.2%) by per-protocol analysis. The eradication rate decreased significantly from 1998 to 2013 (P < 0.001 for both intention-to-treat and per-protocol analyses). Adverse events were reported in 41 studies with 8,018 subjects with an overall incidence rate of 20.4% (95% CI, 19.6%-21.3%). The available data suggest that the effectiveness of standard triple therapy for H. pylori eradication has decreased to an unacceptable level. A novel therapeutic strategy is warranted to improve the effectiveness of first-line treatment for H. pylori infection in Korea.
Alkylating Agents/therapeutic use ; Amoxicillin/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Anti-Ulcer Agents/therapeutic use ; Clarithromycin/therapeutic use ; *Communicable Disease Control ; Cytochrome P-450 CYP3A Inhibitors/therapeutic use ; *Disease Eradication ; *Drug Resistance, Bacterial ; Drug Therapy, Combination ; Gastritis/microbiology/pathology ; Helicobacter Infections/*drug therapy ; Helicobacter pylori ; Humans ; Metronidazole/therapeutic use ; Proton Pump Inhibitors/*therapeutic use ; Republic of Korea ; Tinidazole/therapeutic use

No abstract available.
Amoxicillin/therapeutic use ; Clarithromycin/therapeutic use ; *Communicable Disease Control ; *Disease Eradication ; *Drug Resistance, Bacterial ; Helicobacter Infections/*drug therapy ; Helicobacter pylori ; Humans ; Metronidazole/therapeutic use ; Republic of Korea ; Tinidazole/therapeutic use

This study is to prepare the in situ forming sustained-release injection which can perform sustained release behavior at the periodontal site for 7 days and to evaluate its in vitro and in vivo properties. After preparation of in situ forming sustained-release injection the in situ time was studied. And the surface of the solid injection was characterized by SEM. The rheological curve at 0 degrees C, 25 degrees C, 37 degrees C was determined and the impact of the temperature on the viscosity was examined. The in vitro release behavior was investigated. At last, rabbit periodontitis model was established to study its pharmacokinetics. The injection was stable, hard to stratify and decompose. The in situ forming time was about 6 seconds. It can easily adhere into periodontal pockets. There were lots of holes on the surface of the solid injection for the drug to diffuse. The drug releasing curves could be fit by Korsmeyer-Peppas equation. The drug smoothly released for 7 days at pH 7.4 PBS buffer with a very slight burst release and maintained a certain concentration. In vivo pharmacokinetics results indicated that after administration with the in situ forming injection, achievement of tinidazole (TNZ) concentration in gingival crevicular fluid (GCF) was more comparable and long-lasting than usual solution of TNZ management and relatively constant TNZ levels were attained until 168 h. All these results supported the prospect of tinidazole in situ forming sustained-release injection in clinical applications.
Animals ; Antitrichomonal Agents ; administration & dosage ; pharmacokinetics ; Delayed-Action Preparations ; Drug Carriers ; Drug Compounding ; methods ; Endotoxins ; Gingival Crevicular Fluid ; metabolism ; Injections ; Periodontal Pocket ; metabolism ; Periodontitis ; chemically induced ; metabolism ; Polyesters ; chemical synthesis ; pharmacokinetics ; Polyethylene Glycols ; chemical synthesis ; pharmacokinetics ; Rabbits ; Random Allocation ; Rheology ; Tinidazole ; administration & dosage ; pharmacokinetics

PURPOSE: In a previous study, we have shown that anticancer agents inhibiting topoisomerases improve survival of tumor cells under hypoxic condition. In the present study, we evaluated whether and how cell survival effect of the anticancer agents under hypoxic conditions could be eliminated by the addition of nitroimidazoles, a class of bioreductive agents. METHODS: Human hepatocellular carcinoma cells (HepG2) were incubated with different combinations of pimonidazole (1~1,000 microg/ml) and doxorubicin (0.1 or 1 microg/ml) concentrations under different O2 concentrations [1, 3, 5, 10 and 21 O2]. Then cell numbers, glucose concentrations and lactic acid concentrations in the medium were measured, and DNA fragmentation assay was performed. Finally, different combinations of nitroimidazoles, such as pimonidazole, misonidazole, etanidazole, tinidazole, metronidazole, ornidazole or dimetridazole, and anticancer agents, such as doxorubicin, campothecin, epirubicin, dactinomycin, etoposide or mitomycin C was added to the cell culture medium under hypoxic conditions (1% O2). RESULTS: Pimonidazole at a concentration of 100 microg/ml eliminated cell survival effect of doxorubicin at the concentrations of 0.1 and 1 microg/ml under hypoxic condition (1% O2) by promoting apoptosis. Almost all the cells died even after 24 hours of incubation for all the oxygen concentrations at a combination of 100 microg/ml pimonidazole and 1 microg/ml doxorubicin. Finally, pimonidazole at a concentration of 100 microg/ml, and misonidazole or etanidazole at a concentration of 1,000 microg/ml eliminated cell survival effect of all the anticancer agents tested under hypoxic condition. CONCLUSION: Combination therapy of doxorubicin (adriamycin) with pimonidazole can maximize dororubicin efficacy by eliminating cell survival effect of doxorubicin under hypoxic conditions in treating solid tumors, such as breast cancer.
Anoxia ; Antineoplastic Agents ; Apoptosis ; Breast Neoplasms ; Carcinoma, Hepatocellular ; Cell Count ; Cell Culture Techniques ; Cell Survival ; Dactinomycin ; Dimetridazole ; DNA Fragmentation ; Doxorubicin ; Epirubicin ; Etanidazole ; Etoposide ; Glucose ; Humans ; Lactic Acid ; Metronidazole ; Misonidazole ; Mitomycin ; Nitroimidazoles ; Ornidazole ; Oxygen ; Tinidazole

The objective of this study was to prepare a biodegradable poly (DL-lactide) injectable gel of tinidazole. The formulation parameters evaluated in this study included polymer molecular weight, polymer concentration, solvent and drug loading, and orthogonal design was used to optimize the formulation. The preferable formulation was that 30% (w/w) poly(DL-lactide) (MW is 5 700) dissolved in 70% (w/w) N-methyl-2-pyrrolidone with 4%-6% (w/w) tinidazole.
Delayed-Action Preparations ; Drug Carriers ; chemistry ; Gels ; Lactic Acid ; chemistry ; Polyesters ; Polymers ; chemistry ; Technology, Pharmaceutical ; methods ; Tinidazole ; administration & dosage

OBJECTIVETo determine the dynamic release of tinidazole from the degradable poly-lactic acid (PLLA)-tinidazole blend gel (a periodontal local drug delivery) by high-performance liquid chromatography (HPLC) in vitro and to observe the polylactic acid (as a vector of tinidazole) how to affect the release of tinidazole.

METHODSHPLC analysis was conducted. The operating conditions were C18-ODS-A column, water-methanol-acetic acid as mobile phase at a flow rate of 1.5 ml/min and a detection wavelength at 310 nm and a column temperature at 30 degrees C.

RESULTSThe retention time of tinidazole was about 12 min. There was good linear relationship between the concentrations of tinidazole in blend gel and their peak areas in the ranges of 5 - 500 mg/L. The regression reaction was y = 0.836 + 8.452 2 x 10(-5) x (r = 0.998 6). RSD was 0.2%. Polylactic acid had no influence on the determination of tinidazole. The daily average release of tinidazole was 5.60%. The cumulative release of tinidazole was about 78.40% in 14 days.

CONCLUSIONThe in vitro drug release analysis is an useful method in evaluating the performance of local drug delivery system. HPLC analysis is a simple and accurate method with good reproducibility.

Chromatography, High Pressure Liquid ; Lactic Acid ; Polyesters ; Polymers ; Reproducibility of Results ; Tinidazole

AIMTo illustrate the non-equilibrium properties of drug permeation through stratum corneum (SC) to provide theory and method for transdermal drug delivery.

METHODSThe system of side-by-side permeation chambers in vitro was isolated, thus conditions for equilibrium state were decided. And a network thermodynamic model was established. Non-equilibrium and leakage experiments were completed with which tinidazole was pattern drug.

RESULTSThe properties of non-equilibrium including: long term to reach equilibrium state; delay-start of the permeation; uncertainty of initial drug permeable flux. The properties of leakage including: degression of drug permeable flux; changeability of permeation time constant.

CONCLUSIONThe permeation cell is believed to be a non-linear and time variable system.

Administration, Cutaneous ; Electroporation ; Epidermis ; metabolism ; Humans ; In Vitro Techniques ; Permeability ; Tinidazole ; administration & dosage ; pharmacokinetics

AIMTo test the enhancing activity and the mechanism of oleyl pyroglutamate used as transdermal enhancer.

METHODSThe penetration-enhancing effects of oleyl pyroglutamate, oleyl alcohol and oleic acid on the three drugs (caffeine, tinidazole and cortisone) were observed; the transdermal enhancing mechanism of oleyl pyroglutamate was studied with the attenuated total reflectance Fourier-transfer infrared spectroscopy(ATR-FTIR) of the human stratum corneum in vivo.

RESULTSThe penetration-enhancing ratio of the three drugs was 7.9 fold, 41.8 fold and 2.8 fold, respectively. The absorptions at 2,800-2,950 cm-1 and 1,642-1,646 cm-1 (amide-I) in the ATR-FTIR spectrum of the stratum were found to be shifted differently following removal of the stratum corneum which was treated with oleyl pyroglutamate.

CONCLUSIONOleyl pyroglutamate showed better penetration-enhancing effect on the penetration of drugs. Its transdermal enhancing mechanism may be that oleyl pyroglutamate induced not only disordering of the stratum corneum lipid, but also change of the secondary structure of keratin.

Administration, Cutaneous ; Adult ; Animals ; Caffeine ; administration & dosage ; pharmacokinetics ; Cortisone ; administration & dosage ; pharmacokinetics ; Fatty Alcohols ; pharmacology ; Humans ; Male ; Mice ; Oleic Acid ; pharmacology ; Pyrrolidonecarboxylic Acid ; analogs & derivatives ; chemistry ; pharmacology ; Skin Absorption ; drug effects ; Tinidazole ; administration & dosage ; pharmacokinetics