RESUMO
Proton pump inhibitors (PPIs) are the most effective treatment for gastroesophageal reflux disease (GERD); however, a considerable number of patients fail to respond to PPI therapy and complain of nocturnal heartburn and sleep disturbance. The aims of this study are to evaluate the treatment pattern of GERD-related medications and their efficacy in relieving nocturnal heartburn. A total of 334 patients with GERD receiving PPI therapy within 6 months were enrolled in a multihospital questionnaire survey from January, 2014 to March, 2015. GERD symptoms and patients' satisfaction were assessed by patient questionnaires, and treatment patterns of GERD-related medications were assessed by investigators. Among the 334 patients, 95.8% used PPI once daily and 58.6% used a half-dose of PPI. The PPI treatment pattern was changed in 26.6% of all patients, of those, 54% of the patients doubled the PPI dose, and 29.2% of the patients switched to another PPI. Approximately 60.3% of all patients were prescribed more than three GERD-related medications. The overall satisfaction rate was 61.8%, and 32.2% of patients experienced nocturnal heartburn and sleep disturbance. In the extended-release PPI group, there were fewer nocturnal symptoms compared with the conventional PPI group (10% vs. 33.7%, respectively, P = 0.027). The use of more than three medications was inversely associated with patients' satisfaction (OR = 0.355, 95% CI; 0.197-0.642, P = 0.001). Most patients were prescribed adjunctive medications other than PPIs; however, patients' satisfaction was inversely associated with multiple drugs. Patients' satisfaction was superior in extended-release PPIs than conventional PPIs for the relief of nocturnal heartburn in Korean patients.
Assuntos
Refluxo Gastroesofágico/tratamento farmacológico , Azia/tratamento farmacológico , Satisfação do Paciente/estatística & dados numéricos , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Preparações de Ação Retardada/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Substituição de Medicamentos/estatística & dados numéricos , Dissonias/etiologia , Feminino , Refluxo Gastroesofágico/complicações , Azia/etiologia , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/administração & dosagem , República da Coreia , Inquéritos e Questionários , Avaliação de Sintomas , Adulto JovemRESUMO
PURPOSE: People with dry skin (xerosis) are common in community pharmacies, but there is no consistent guidance for community pharmacists to evaluate and alleviate dry skin. Through evaluating any difference of the clinical scoring systems of EEMCO guidance between a dermatologist and pharmacists and the efficacy of moisturizers for the treatment of dry skin recommended by community pharmacists, we aim to validate a dry skin guidance through the help of community pharmacists. These results provide insight into how community pharmacists can help patients with dry skin. METHODS: The clinical scoring systems of EEMCO guidance used in this study comprised analog scales, the overall dry skin score (ODS), and the specific symptom sum score (SRRC) system. All pictures of the dry skin scored by pharmacists were visually evaluated by a dermatologist. The efficacy of the moisturizers was determined by the difference of the scales on day 0 and on day 28. RESULTS: In this study, 387 patients with dry skin from 157 community pharmacies were evaluated by pharmacists. Visual scale with divisions, ODS and SRRC that were evaluated by pharmacists on day 0 and day 28 were moderately reliable by a dermatologist. All parameters of dry skin were significantly improved by the moisturizers which were recommended by community pharmacists on day 28. CONCLUSION: Visual scale, ODS and SRRC can be generally measured to evaluate dry skin in community pharmacies with moderate degree of reliability. This finding has possible applications for investigating the assessment of the community pharmacists on clinical scoring system of dry skin and moisturizers.
Assuntos
Dermatologia/normas , Farmácias/normas , Exame Físico/normas , Guias de Prática Clínica como Assunto , Creme para a Pele/farmacologia , Dermatopatias/diagnóstico , Dermatopatias/tratamento farmacológico , Adulto , Relação Dose-Resposta a Droga , Europa (Continente) , Feminino , Humanos , Coreia (Geográfico) , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Dermatopatias/classificação , Resultado do Tratamento , Escala Visual AnalógicaRESUMO
The prevalence of gastroesophageal reflux disease in Korea has been believed to be low, but the incidence of gastroesophageal reflux disease in Korea is expected to increase because of the longer life expectancy and more ingestion of westernized food. The aim of this study was to report differences in the risk factors of reflux esophagitis (RE) according to age in Korea. We prospectively recruited the subjects who had RE among those who visited a health promotion center for upper gastrointestinal cancer surveillance at Hallym Medical Center (five institutions) between January 2008 and February 2009. The enrolled study participants comprised 742 subjects with RE and 1484 healthy controls. The independent risk factors of RE in young and adult group were male sex, smoking, coffee, body mass index ≥ 25, hiatal hernia, and Helicobacter pylori negativity. The risk factors of RE in elderly group were smoking, coffee, and hiatal hernia. The risk factors for RE according to age group were found to differ. In elderly group, Helicobacter pylori infection was not a significant protective factor contrary to young and adult groups.
Assuntos
Esofagite Péptica/epidemiologia , Infecções por Helicobacter/epidemiologia , Hérnia Hiatal/epidemiologia , Sobrepeso/epidemiologia , Fumar/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Café , Estudos de Coortes , Comportamento de Ingestão de Líquido , Esofagite Péptica/diagnóstico , Feminino , Helicobacter pylori , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , República da Coreia/epidemiologia , Fatores de Risco , Fatores Sexuais , Adulto JovemRESUMO
This study aimed to evaluate the long-term efficacy of entecavir (ETV) in adefovir (ADV)-refractory chronic hepatitis B (CHB) patients with prior lamivudine (LMV) resistance. A total of 55 ADV-refractory CHB patients with prior LMV resistance, who received rescue therapy with ETV 1 mg daily for at least 12 months, were consecutively enrolled and analysed. Forty-four patients were men, and their median age was 47 (25-69). Ten patients had liver cirrhosis and 46 patients were positive for hepatitis B e antigen (HBeAg). Median hepatitis B virus DNA levels were 6.6 (4.3-8.0) log(10) copies/mL, and the median duration of ETV therapy was 24 (12-47) months. Cumulative virologic response rates at 6, 12, 24 and 36 months were 18%, 29%, 58% and 75%, respectively. HBeAg loss occurred in 10 (21.7%) of 46 HBeAg-positive patients. In multivariate analysis, only initial virologic response at 3 months remained as an independent predictor for virologic response (RR 3.143; 95% CI 1.387-7.120; P = 0.006). The patients with a virological response at 3 months had not only a significantly higher probability of achieving a virologic response (P < 0.001) but also lower probability of experiencing a virologic breakthrough (P = 0.043) than the patients without an early response. Viral breakthrough was observed in 29 patients during the follow-up period. Cumulative breakthrough rates at 6, 12, 24 and 36 months were 0%, 15%, 45% and 73%, respectively. ETV monotherapy may be considerably efficacious in cases with an initial virological response but its efficacy is attenuated by frequent emergence of ETV resistance in ADV-refractory CHB patients with prior LMV resistance.
Assuntos
Adenina/análogos & derivados , Antivirais/administração & dosagem , Farmacorresistência Viral , Guanina/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Lamivudina/farmacologia , Organofosfonatos/administração & dosagem , Adenina/administração & dosagem , Adulto , Idoso , DNA Viral/sangue , Feminino , Guanina/administração & dosagem , Antígenos de Superfície da Hepatite B/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Salvação/métodos , Resultado do TratamentoRESUMO
Pharmacokinetics of sildenafil and its metabolite, N-desmethylsildenafil, in humans and rats with liver cirrhosis (LC) and diabetes mellitus (DM), alone and in combination (LCD) did not seem to be reported. Sildenafil was administered intravenously (10 mg/kg) and orally (20 mg/kg) to control, LC, DM, and LCD rats. Expression of intestinal CYP isozymes in those rats was also measured. In LC, DM, and LCD rats, the areas under the curve (AUCs) of intravenous sildenafil were significantly greater (by 195%, 54.2%, and 127%, respectively) than controls. In LC and LCD rats, AUCs of oral sildenafil were significantly greater (3010% and 2030%, respectively) than controls. In LC, DM, and LCD rats, significantly greater AUCs of intravenous sildenafil were due to the slower hepatic extraction of sildenafil (because of decrease in the protein expression of hepatic CYP2C11 and 3A subfamily in LC and LCD rats, and CYP2C11 in DM rats). In LC and LCD rats, greater magnitude of increase in AUCs of oral sildenafil than those after the intravenous administration could be mainly due to the decrease in the intestinal extraction of sildenafil (because of decrease in the protein expression of intestinal CYP2C11 in LC and LCD rats).
Assuntos
Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Cirrose Hepática/complicações , Cirrose Hepática/metabolismo , Piperazinas/farmacocinética , Sulfonas/farmacocinética , Vasodilatadores/farmacocinética , Administração Oral , Animais , Proteínas Sanguíneas/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos , Immunoblotting , Injeções Intravenosas , Intestinos/enzimologia , Masculino , Microssomos Hepáticos/metabolismo , Piperazinas/administração & dosagem , Piperazinas/sangue , Piperazinas/química , Ligação Proteica , Purinas/administração & dosagem , Purinas/sangue , Purinas/química , Purinas/farmacocinética , Ratos , Ratos Sprague-Dawley , Citrato de Sildenafila , Sulfonas/administração & dosagem , Sulfonas/sangue , Sulfonas/química , Vasodilatadores/administração & dosagem , Vasodilatadores/sangue , Vasodilatadores/químicaRESUMO
The chemical stage of the Monte Carlo track-structure simulation code Geant4-DNA has been revised and validated. The root-mean-square (RMS) empirical parameter that dictates the displacement of water molecules after an ionization and excitation event in Geant4-DNA has been shortened to better fit experimental data. The pre-defined dissociation channels and branching ratios were not modified, but the reaction rate coefficients for simulating the chemical stage of water radiolysis were updated. The evaluation of Geant4-DNA was accomplished with TOPAS-nBio. For that, we compared predicted time-dependentGvalues in pure liquid water for·OH, e-aq, and H2with published experimental data. For H2O2and H·, simulation of added scavengers at different concentrations resulted in better agreement with measurements. In addition, DNA geometry information was integrated with chemistry simulation in TOPAS-nBio to realize reactions between radiolytic chemical species and DNA. This was used in the estimation of the yield of single-strand breaks (SSB) induced by137Csγ-ray radiolysis of supercoiled pUC18 plasmids dissolved in aerated solutions containing DMSO. The efficiency of SSB induction by reaction between radiolytic species and DNA used in the simulation was chosen to provide the best agreement with published measurements. An RMS displacement of 1.24 nm provided agreement with measured data within experimental uncertainties for time-dependentGvalues and under the presence of scavengers. SSB efficiencies of 24% and 0.5% for·OH and H·, respectively, led to an overall agreement of TOPAS-nBio results within experimental uncertainties. The efficiencies obtained agreed with values obtained with published non-homogeneous kinetic model and step-by-step Monte Carlo simulations but disagreed by 12% with published direct measurements. Improvement of the spatial resolution of the DNA damage model might mitigate such disagreement. In conclusion, with these improvements, Geant4-DNA/TOPAS-nBio provides a fast, accurate, and user-friendly tool for simulating DNA damage under low linear energy transfer irradiation.
Assuntos
Dano ao DNA , Água , Simulação por Computador , Transferência Linear de Energia , Método de Monte CarloRESUMO
BACKGROUND: There have been still few valuable markers that can be used as indirect markers of liver fibrosis in chronic hepatitis B. AIMS: This study aimed to evaluate efficacy of several indirect markers of liver fibrosis and to identify the most valuable test in chronic hepatitis B. PATIENTS AND METHODS: A total of 264 patients with chronic hepatitis B were consecutively enrolled. Fibrosis was staged by a single blinded pathologist according to the METAVIR system. Significant fibrosis was defined as stage >or=2. We investigated diagnostic accuracy of four indirect markers including aspartate aminotransferase to platelet ratio index for predicting significant fibrosis. RESULTS: Mean age was 28 years. 53% (141/264) had significant hepatic fibrosis. Of indirect markers, aspartate aminotransferase to platelet ratio index yielded the best area under the receiver operating characteristic curve (0.86; 95% confidence interval, 0.82-0.91). Positive predictive value/negative predictive value at 0.5, 1.5 and 2.0 of aspartate aminotransferase to platelet ratio index score for predicting significant fibrosis were 63%/91%, 83%/74% and 86%/65%, respectively. The odds ratio for aspartate aminotransferase to platelet ratio index >or=1.4 relative to less than aspartate aminotransferase to platelet ratio index of 1.4 was 17.971 (p<0.0001; 95% confidence interval, 9.677-33.376). CONCLUSIONS: Of simple markers already developed in chronic hepatitis C, aspartate aminotransferase to platelet ratio index may be the most accurate and simple marker for predicting significant fibrosis in chronic hepatitis B.
Assuntos
Aspartato Aminotransferases/sangue , Biomarcadores , Hepatite B Crônica/sangue , Hepatite B Crônica/patologia , Cirrose Hepática/sangue , Adolescente , Adulto , Biópsia por Agulha , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Valor Preditivo dos Testes , Curva ROCRESUMO
This Special Report presents a description of Geant4-DNA user applications dedicated to the simulation of track structures (TS) in liquid water and associated physical quantities (e.g., range, stopping power, mean free path ). These example applications are included in the Geant4 Monte Carlo toolkit and are available in open access. Each application is described and comparisons to recent international recommendations are shown (e.g., ICRU, MIRD), when available. The influence of physics models available in Geant4-DNA for the simulation of electron interactions in liquid water is discussed. Thanks to these applications, the authors show that the most recent sets of physics models available in Geant4-DNA (the so-called "option4" and "option 6" sets) enable more accurate simulation of stopping powers, dose point kernels, and W-values in liquid water, than the default set of models ("option 2") initially provided in Geant4-DNA. They also serve as reference applications for Geant4-DNA users interested in TS simulations.
RESUMO
OBJECTIVE: To evaluate the short- and long-term efficacy and safety of abciximab and cilostazol in patients with acute MI and unstable angina undergoing intracoronary stenting. METHODS: Acute-phase (7 and 30 days), 6-month and long-term composite outcomes involving death, myocardial infarction or urgent target vessel revascularization (TVR) together with other outcomes (composite outcomes involving death, MI and elective TVR with restenosis and stroke) were evaluated retrospectively in a total of 175 patients. Safety outcomes were assessed using data on the incidence of bleeding and thrombocytopenia at Day 7 and Day 30. RESULTS: Of 175 patients, 83 (47.4%) patients received abciximab. At 7 and 30 days, the composite outcome for the group treated with cilostazol alone and that treated with abciximab in combination with cilostazol did not differ significantly. The composite outcomes at 6 months and 1 year were significantly lower in the abciximab plus cilostazol group (relative risk 0.35, 95% Cl 0.13 - 0.90, relative risk 0.28, 95% CI 0.10 -0.78, respectively). The incidence of major bleeding at the access-site and in the gastrointestinal tract and minor bleeding were significantly higher in the group receiving abciximab plus cilostazol group at 7 days (relative risk 3.33, 95% CI 1.66 - 6.65, relative risk 9.98, 95% CI 1.29 - 77.07, relative risk 1.96, 95% CI 1.06 - 3.62, respectively) and at 30 days (relative risk 3.33, 95% CI 1.66 - 6.65, relative risk 5.54, 95% CI 1.25 - 24.56, relative risk 1.96, 95% CI 1.06 - 3.62, respectively). CONCLUSION: The combination of abciximab and cilostazol showed an improvement in major cardiac incidents at 6 months and 1 year of the treatment when compared to the group receiving cilostazol alone. However, abciximab did not improve the incidence of death but increased the risk of bleeding complications.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Stents , Tetrazóis/efeitos adversos , Tetrazóis/uso terapêutico , Trombose/prevenção & controle , Abciximab , Idoso , Angina Instável/complicações , Angina Instável/cirurgia , Cilostazol , Angiografia Coronária , Reestenose Coronária/epidemiologia , Reestenose Coronária/prevenção & controle , Quimioterapia Combinada , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/cirurgia , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia , Resultado do TratamentoRESUMO
A bioequivalence study of diclofenac injection (test formulation (diclofenac potassium): HANA, reference formulation (diclofenac sodium): Shinpoong) was conducted in 18 healthy male Korean volunteers who received each medicine at a dose of 75 mg in a 2 x 2 crossover study. There was a one-week washout period between the doses. Plasma concentrations of diclofenac were monitored by high-performance liquid chromatography over a period of 24 hours after the i.m. injection. AUC0-24 (the area under the plasma concentration-time curve from time 0-24 hours) was calculated by the linear-log trapezoidal method. Cmax (maximum plasma drug concentration) and tmax (time to reach Cmax) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC0-24 and Cmax, and non-transformed tmax. There were no significant differences between the medications in AUC0-24 and Cmax. The point estimates and 90% confidence intervals for AUC0-24 (parametric) and Cmax (parametric) were 0.973 (0.8971 to 1.0557) and 0.993 (0.9452-1.0451), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration Guidelines. The corresponding value for tmax was 0.75 (0.00 to 1.00). Moreover, the modified Pitman-Morgan's adjusted F-test indicated that the bioavailabilities of diclofenac in the two medications were comparable regarding intra- and interindividual variability. Therefore, these results indicate that the two medications of diclofenac are bioequivalent and, thus, may be prescribed interchangeably.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Inibidores de Ciclo-Oxigenase/farmacocinética , Diclofenaco/farmacocinética , Adulto , Anti-Inflamatórios não Esteroides/sangue , Estudos Cross-Over , Inibidores de Ciclo-Oxigenase/sangue , Diclofenaco/sangue , Humanos , Injeções Intravenosas , Coreia (Geográfico) , Masculino , Equivalência TerapêuticaRESUMO
Because physiological changes occurring in diabetes mellitus patients could alter the pharmacokinetics and pharmacodynamics of the drugs used to treat the disease, the pharmacokinetics and pharmacodynamics of azosemide were investigated after intravenous and oral administration of the drug (10 mg kg-1) to control and alloxan-induced diabetes mellitus rats (AIDRs). After intravenous administration of azosemide to the AIDRs, the area under the plasma concentration-time curve (AUC) increased considerably (3120 compared with 2520 micrograms min mL-1; P < 0.135) and the total body clearance decreased considerably (3.20 compared with 3.96 mL min-1 kg-1; P < 0.0593). The considerable reduction in time-averaged total body clearance in the AIDRs was a result of the significant decrease in renal clearance (1.01 compared with 1.55 mL min-1 kg-1) in the AIDRs, the non-renal clearance being comparable between the two groups of rats. After intravenous administration, the 8-h urinary excretion of azosemide (29.5 compared with 40% of intravenous dose; P < 0.0883) and one of its metabolites, M1 (2.15 compared with 2.60% of intravenous dose, expressed in terms of azosemide; P < 0.05) decreased in the AIDRs because of the impaired kidney function. The diuretic, natriuretic, kaliuretic and chloruretic efficiencies increased significantly in the AIDRs. After oral administration of azosemide, AUC decreased significantly in the AIDRs (115 compared with 215 micrograms min mL-1) possibly because of the reduced gastrointestinal absorption of azosemide in the AIDRs. After oral administration of azosemide, the 8-h urine output decreased significantly in the AIDRs (9.32 compared with 16.1 mL per 100 g body weight) because of the significantly reduced 8-h urinary excretion of azosemide (3.00 compared with 9.14% of oral dose). After both intravenous and oral administration some pharmacokinetic and pharmacodynamic parameters of azosemide were significantly different in AIDRs.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Diuréticos/farmacocinética , Sulfanilamidas/farmacocinética , Administração Oral , Aloxano , Animais , Injeções Intravenosas , Ratos , Ratos Sprague-Dawley , Sulfanilamidas/administração & dosagem , Sulfanilamidas/farmacologiaRESUMO
Atenolol is a selective ß1 receptor antagonist that is available as a racemic mixture. The objective of this study was to compare the pharmacokinetics and evaluate the bioequivalence of 50 mg atenolol test and reference formulations in 24 healthy Korean male volunteers.This study was a single-dose, randomized, open-label, 2 period crossover study. 24 healthy Korean male volunteers randomly received 50 mg of either test or reference atenolol formulations in a 2×2 crossover study. There was a 1 week washout period between doses. The area under the curve (AUC)0-24 h and Cmax of 50 mg atenolol were the primary criteria for evaluation of bioequivalence.The mean ± standard deviation (SD) values of the Cmax, Tmax, AUC0-24 h, AUC0-∞, ke, and t1/2 of the test and reference formulations were 268.4 (78.96) and 256.9 (79.34), 2.750 (0.9555) and 3.104 (1.053), 1 981 (729.2) and 1 872 (604.8), 2228 (697.1) and 2 187 (628.5), 0.1332 (0.02748) and 0.1421 (0.04223), 5.419 (1.110) and 5.442 (2.357), respectively. The 90% confidence intervals for AUC0-24 h and Cmax were 0.9037-1.166 and 0.9169-1.1987, respectively. These results were within the accepted bioequivalence range of 0.80-1.25, which satisfied the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration guidelines. In conclusion, the findings of this study indicate that the 2 formulations of 50 mg atenolol that were tested are bioequivalent. Therefore, these formulations may be prescribed interchangeably.
Assuntos
Atenolol/farmacocinética , Adulto , Área Sob a Curva , Atenolol/administração & dosagem , Atenolol/efeitos adversos , Atenolol/sangue , Química Farmacêutica , Estudos Cross-Over , Humanos , Masculino , República da Coreia , Comprimidos/administração & dosagem , Comprimidos/efeitos adversos , Comprimidos/farmacocinética , Equivalência Terapêutica , Adulto JovemRESUMO
BACKGROUND: The eradication rates of Helicobacter pylori (H. pylori) using a proton pump inhibitor (PPI)-based triple therapy have declined due to antibiotic resistance worldwide. AIM: To compare the eradication rate of the 10-day sequential therapy for H. pylori infection with that of the 14-day standard PPI-based triple therapy. METHODS: This was a prospective, randomised, controlled study. A total of 409 patients with H. pylori infection were randomly assigned to receive either the 10-day sequential therapy regimen, which consisted of pantoprazole (40 mg) plus amoxicillin (1000 mg) twice a day for 5 days, then pantoprazole (40 mg) with clarithromycin (500 mg) and metronidazole (500 mg) twice a day for another five consecutive days or the 14-day PPI-based triple therapy regimen, which consisted of pantoprazole (40 mg) with amoxicillin (1000 mg) and clarithromycin (500 mg) twice a day for 14 days. The pre- and post-treatment H. pylori status were assessed by rapid urease test, urea breath test, or histology. Successful eradication was confirmed at least 4 weeks after finishing the treatment. RESULTS: In the intention-to-treat analysis, the eradication rates of the 10-day sequential therapy and of the 14-day PPI-based triple therapy were 85.9% (176/205) and 75.0% (153/205), respectively (P = 0.006). In the per-protocol analysis, the eradication rates were 92.6% (175/205) and 85% (153/204), respectively (P = 0.019). There was no statistically significant difference between the two investigated groups regarding the occurrence of adverse event rates (18.9% vs. 13.3%, P = 0.143). CONCLUSION: The 10-day sequential therapy achieved significantly higher eradication rates than the 14-day standard PPI-based triple therapy in Korea.
Assuntos
Antibacterianos/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Inibidores da Bomba de Prótons/administração & dosagem , 2-Piridinilmetilsulfinilbenzimidazóis/administração & dosagem , Adulto , Amoxicilina/administração & dosagem , Testes Respiratórios , Claritromicina/administração & dosagem , Interpretação Estatística de Dados , Esquema de Medicação , Quimioterapia Combinada , Feminino , Helicobacter pylori , Humanos , Masculino , Metronidazol/administração & dosagem , Pessoa de Meia-Idade , Pantoprazol , Estudos Prospectivos , República da Coreia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: The incidence of diabetes mellitus is increased in patients with liver cirrhosis. Oltipraz is currently in trials to treat patients with liver fibrosis and cirrhosis induced by chronic hepatitis types B and C and is primarily metabolized via hepatic cytochrome P450 isozymes CYP1A1/2, 2B1/2, 2C11, 2D1 and 3A1/2 in rats. We have studied the influence of diabetes mellitus on pharmacokinetics of oltipraz and on expression of hepatic, CYP1A, 2B1/2, 2C11, 2D and 3A in rats with experimental liver cirrhosis. EXPERIMENTAL APPROACH: Oltipraz was given intravenously (10 mg x kg(-1)) or orally (30 mg x kg(-1)) to rats with liver cirrhosis induced by N-dimethylnitrosamine (LC rats) or with diabetes, induced by streptozotocin (DM rats) or to rats with both liver cirrhosis and diabetes (LCD rats) and to control rats, and pharmacokinetic variables measured. Protein expression of hepatic CYP1A, 2B1/2, 2C11, 2D and 3A was measured using Western blot analysis. KEY RESULTS: After i.v. or p.o. administration of oltipraz to LC and DM rats, the AUC was significantly greater and smaller, respectively, than that in control rats. In LCD rats, the AUC was that of LC and DM rats (partially restored towards control rats). Compared with control rats, the protein expression of hepatic CYP1A increased, that of CYP2C11 and 3A decreased, but that of CYP2B1/2 and 2D was not altered in LCD rats. CONCLUSIONS AND IMPLICATIONS: In rats with diabetes and liver cirrhosis, the AUC of oltipraz was partially restored towards that of control rats.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Cirrose Hepática Experimental/metabolismo , Pirazinas/farmacocinética , Esquistossomicidas/farmacocinética , Animais , Área Sob a Curva , Sistema Enzimático do Citocromo P-450/biossíntese , Diabetes Mellitus Experimental/complicações , Fígado/enzimologia , Cirrose Hepática Experimental/complicações , Ratos , Tionas , TiofenosRESUMO
OBJECTIVE: To evaluate the effect of raloxifene on bone mineral density (BMD) and serum lipid levels in post-menopausal women who had discontinued hormone replacement therapy (HRT). METHODS: Thirty-four post-menopausal women with low BMD who had taken 60 mg of raloxifene daily for 12 months after discontinuing HRT were evaluated retrospectively. Information about their demographics, fracture history, BMD, lipid profiles and adverse events were collected from medical records and intranet database. The outcome measures were changes in the spine (L2-L4) and femur BMD, serum lipid concentrations, fracture rate and tolerability. RESULTS: The post-menopausal women had a significant increase in their spine (L2-L4) and femur BMD from their baseline BMD [spine, 2.9 +/- 4.6% (P < 0.001); femur, 3.0 +/- 6.6% (P = 0.01)]. Serum low-density lipoprotein (LDL) cholesterol was significantly reduced by 22.6% below baseline after 12 months (P = 0.007). No fractures were observed during therapy. Raloxifene was well tolerated. The most common adverse event was hot flash, which was generally mild. CONCLUSIONS: Raloxifene increases BMD at important skeletal sites, and lowers LDL cholesterol with tolerable adverse events.
Assuntos
Densidade Óssea/efeitos dos fármacos , Lipídeos/sangue , Osteoporose Pós-Menopausa/prevenção & controle , Pós-Menopausa/metabolismo , Cloridrato de Raloxifeno/uso terapêutico , Absorciometria de Fóton , Idoso , Índice de Massa Corporal , Terapia de Reposição de Estrogênios , Feminino , Fraturas Ósseas/prevenção & controle , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Cloridrato de Raloxifeno/farmacologia , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND AND STUDY AIMS: It is difficult to achieve complete endoscopic resection of rectal carcinoid tumors without any procedure-related complications. In this study, we evaluated the efficacy and safety of endoscopic submucosal resection with double ligation (ESMR-DL) for the treatment of small rectal carcinoid tumors. PATIENTS AND METHODS: Eleven rectal carcinoid tumors (in 11 patients) were resected by ESMR-DL between November 2001 and April 2004, using a conventional single-channel endoscope with an attached band-ligator device. The lesion was aspirated into the ligator device and an elastic band was placed around the base; a detachable snare was then used to ligate the stalk below the elastic band; and snare resection was performed above the elastic band. The resected specimens were examined with respect to size, histological atypia, depth of invasion, and the histological appearance of the resection margins. RESULTS: All the lesions were excised completely without any complications. There was no tumor invasion beyond the submucosal layer and there was no evidence of atypia in any of the specimens. Tumor diameter varied from 2.0 mm to 10.0 mm (average 6.2 mm). None of the 11 specimens showed histopathological evidence of tumor involvement at the resection margins. There were no immediate or late complications (bleeding or perforation) after ESMR-DL. There was no local recurrence and there were no distant metastases in any patients during the mean follow-up period of 18 months. CONCLUSION: Endoscopic submucosal resection with double ligation is a useful and safe method for the treatment of small rectal carcinoid tumors.
Assuntos
Tumor Carcinoide/cirurgia , Endoscopia Gastrointestinal/métodos , Neoplasias Retais/cirurgia , Tumor Carcinoide/patologia , Corantes , Feminino , Humanos , Índigo Carmim , Ligadura , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Retais/patologia , Resultado do TratamentoRESUMO
A high-performance liquid chromatographic method was developed for the determination of aloesin in human plasma. The method involved deproteinization of biological samples with 1 volume of each 0.04 M Ba(OH)2 and 10% ZnSO4 aqueous solution. A 50-microliter aliquot of the supernatant was injected onto a C18 reversed-phase column. The mobile phase, methanol-H2O (20:80, v/v), was run at a flow-rate 1.5 ml/min. The column effluent was monitored by a ultraviolet detector at 254 nm. The retention time of aloesin was 7 min. The detection limit for aloesin in human plasma was 0.1 microgram/ml. The coefficient of variation of the assay was generally low (below 5.04%) for human plasma. No interferences from endogenous substances were observed.
Assuntos
Cromonas/sangue , Glucosídeos/sangue , Animais , Cromatografia Líquida de Alta Pressão , Cromonas/farmacocinética , Glucosídeos/farmacocinética , Humanos , Ratos , Ratos Sprague-Dawley , Sensibilidade e Especificidade , Espectrofotometria UltravioletaRESUMO
The pharmacokinetics of vancomycin were evaluated simultaneously using both arterial and venous plasma data in five rabbits after a rapid bolus intravenous (i.v.) dosing. Initial arterial to venous concentration ratios at 5 s after i.v. injection were the highest, with values of 27.1, 36.2, 36.6, 43.7 and 29.7 for rabbits 1-5, respectively. This could be the result of diffusion of vancomycin from the arterial plasma into the extravascular tissues. Both curves decayed in parallel at the terminal phase with the venous levels higher than the arterial levels by 23, 37, 34, 13 and 14% for rabbits 1-5, respectively. This difference could be the result of continuous release of vancomycin from the extravascular tissues to the venous blood. Detailed analysis showed differences in various pharmacokinetic parameters based on arterial and venous data. For example, values for venous Vc were 9.2, 11, 1.9, 7.2 and 8.8 times greater than the arterial values for rabbits 1-5, respectively. The values for both venous Vss and MRT were higher than those of the arterial values in all five rabbits studied. This could be due to more extensive distribution of vancomycin in the extravascular tissues. A plot of 1/Q (urine flow rate) versus 1/ClR of vancomycin yielded a straight line in rabbits 6-10, indicating that the renal clearance of vancomycin in rabbits is dependent upon urine flow.
Assuntos
Coleta de Amostras Sanguíneas/métodos , Vancomicina/farmacocinética , Animais , Artérias , Infusões Intravenosas , Injeções Intravenosas , Rim/metabolismo , Masculino , Coelhos , Vancomicina/sangue , Vancomicina/urina , VeiasRESUMO
The pharmacokinetics of azosemide were evaluated simultaneously using both arterial and venous plasma data in six rabbits after a rapid 5 s intravenous bolus dosing. Initial arterial to venous ratios at 5 s after injection were the highest with values of 81.1, 67.3, 58.7, 530, 2660, and 10.5 for rabbits 1-6, respectively. Both curves decayed, paralleling each other at the terminal phase, with the venous levels higher than the arterial levels by 15.3, 31.9, 34.1, 40.7, 30.5, and 16.5% for rabbits 1-6, respectively. An exponential term with a negative coefficient was used to account for the short and steep rising phase of venous plasma levels after injection. Detailed analysis showed significant differences in various pharmacokinetic parameters, such as initial volume of distribution, apparent volume of distribution at steady state, and mean residence time based on arterial or venous data. A plot of 1/Q (urine flow rate) versus 1/CLR (renal clearance) of azosemide yielded a straight line in six rabbits, indicating that the CLR of azosemide is urine flow dependent in rabbits.
Assuntos
Diuréticos/farmacocinética , Sulfanilamidas/farmacocinética , Animais , Artérias , Cromatografia Líquida de Alta Pressão , Diuréticos/sangue , Diuréticos/urina , Meia-Vida , Injeções Intravenosas , Masculino , Taxa de Depuração Metabólica , Coelhos , Software , Sulfanilamidas/sangue , Sulfanilamidas/urina , VeiasRESUMO
Various factors influencing the protein binding of vancomycin were examined using equilibrium dialysis method. Four per cent human serum albumin (HSA) and/or 0.08 per cent alpha-1-acid glycoprotein (AAG), dissolved in isotonic phosphate buffer, were dialyzed against isotonic phosphate buffer of pH 7.4 using Spectrapor 2 membrane. The protein binding of vancomycin to 0.08 per cent AAG was dependent on vancomycin concentrations; the values ranged from 21.1 per cent at the vancomycin concentration of 20 micrograms ml-1 to 5.30 per cent at 2400 micrograms ml-1. However, binding to 4 per cent HSA was relatively constant, 8.79 +/- 2.43 per cent over a vancomycin concentration range of 20-2400 micrograms ml-1. The values to 4 per cent HSA alone and 0.08 per cent AAG alone did not predict the greater binding of vancomycin in the presence of both proteins, especially at higher concentrations of vancomycin; the values to 4 per cent HSA with 0.08 per cent AAG were constant, 26.3 +/- 3.74 per cent, at the vancomycin concentration range of 20-2400 micrograms ml-1. This suggested an interaction between the proteins, which resulted in enhanced binding of vancomycin. The protein binding of vancomycin to 4 per cent HSA with 0.08 per cent AAG was not influenced by the different incubation temperatures (4 degrees, 22 degrees, and 37 degrees), quantities of heparin (up to 40 units ml-1) or AAG (up to 0.16 per cent), or buffers (isotonic phosphate buffer of pH 7.4, phosphate buffer of pH 7.4 and 0.9 per cent NaCl solution) at the vancomycin concentration of 80 micrograms ml-1. Vancomycin was found to be stable in human serum albumin or in isotonic phosphate buffer of pH 7.4.