RESUMO
OBJECTIVE: To assess whether adding metoclopramide to a protocol of maropitant and pantoprazole would reduce incidence of ptyalism, vomiting and regurgitation in brachycephalic dogs undergoing thoracolumbar spinal surgery. STUDY DESIGN: Randomized blinded controlled trial. ANIMALS: A total of 43 brachycephalic dogs undergoing thoracolumbar spinal surgery. METHODS: In addition to a standardized anaesthetic regimen, dogs were randomized to be administered either a 2 mg kg-1 day-1 metoclopramide constant rate infusion (CRI) or a saline solution at an equivalent infusion rate, started after anaesthetic induction and discontinued 5 hours after tracheal extubation. The presence of vomiting, regurgitation and pytalism, and short form of the Glasgow Composite Pain Scale pain scores were assessed by a blinded observer hourly for 4 hours, starting 1 hour postextubation. RESULTS: Regurgitation occurred in six dogs postoperatively; three dogs were in the placebo group and three in the metoclopramide group. The odds ratio (OR) of regurgitation after surgery did not differ between groups [OR: 0.76, 95% confidence interval (CI): 0.13-4.3, p = 0.76]. The odds of observing ptyalism at 3 and 4 hours was approximately 15 times less than 1 hour postoperatively (both OR: 15.4, 95% CI: 1.8-130.7, p = 0.012) and did not differ based on the addition of metoclopramide (OR: 0.73, 95% CI: 0.07-8.0, p = 0.79). The odds of observing pain did not change over time and did not differ based on the addition of metoclopramide (OR: 0.71, 95% CI: 0.12-4.2, p = 0.71). Vomiting did not occur during the study (0.0%, 95% CI: 0.0-8.2%). No adverse effects were observed during the study period in either group. CONCLUSIONS AND CLINICAL RELEVANCE: The addition of a metoclopramide CRI to maropitant and pantoprazole did not result in a significant reduction in ptyalism or regurgitation in brachycephalic dogs undergoing thoracolumbar spinal surgery.
Assuntos
Antieméticos , Doenças do Cão , Metoclopramida , Animais , Cães , Metoclopramida/administração & dosagem , Metoclopramida/uso terapêutico , Antieméticos/administração & dosagem , Antieméticos/uso terapêutico , Masculino , Feminino , Doenças do Cão/cirurgia , Doenças do Cão/prevenção & controle , Craniossinostoses/cirurgia , Craniossinostoses/veterinária , Náusea e Vômito Pós-Operatórios/veterinária , Náusea e Vômito Pós-Operatórios/prevenção & controle , Refluxo Laringofaríngeo/veterinária , Refluxo Laringofaríngeo/prevenção & controle , Quinuclidinas/administração & dosagem , Quinuclidinas/uso terapêutico , Pantoprazol/administração & dosagem , Pantoprazol/uso terapêutico , Pantoprazol/farmacologiaRESUMO
Pantoprazole is a proton pump inhibitor indicated for the treatment of gastroesophageal reflux disease, a condition that disproportionately affects children with obesity. Appropriately dosing pantoprazole in children with obesity requires understanding the body size metric that best guides dosing, but pharmacokinetic (PK) trials using traditional techniques are limited by the need for larger sample sizes and frequent blood sampling. Physiologically-based PK (PBPK) models are an attractive alternative that can account for physiologic-, genetic-, and drug-specific changes without the need for extensive clinical trial data. In this study, we explored the effect of obesity on pantoprazole PK and evaluated label-suggested dosing in this population. An adult PBPK model for pantoprazole was developed using data from the literature and accounting for genetic variation in CYP2C19. The adult PBPK model was scaled to children without obesity using age-associated changes in anatomical and physiological parameters. Lastly, the pediatric PBPK model was expanded to children with obesity. Three pantoprazole dosing strategies were evaluated: 1 mg/kg total body weight, 1.2 mg/kg lean body weight, and US Food and Drug Administration-recommended weight-tiered dosing. Simulated concentration-time profiles from our model were compared with data from a prospective cohort study (PAN01; NCT02186652). Weight-tiered dosing resulted in the most (>90%) children with pantoprazole exposures in the reference range, regardless of obesity status or CYP2C19 phenotype, confirming results from previously published population PK models. PBPK models may allow for the efficient study of physiologic and developmental effects of obesity on PK in special populations where clinical trial data may be limited.
Assuntos
Citocromo P-450 CYP2C19 , Pantoprazol , Obesidade Infantil , Inibidores da Bomba de Prótons , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Citocromo P-450 CYP2C19/genética , Variação Genética , Modelos Biológicos , Pantoprazol/farmacocinética , Pantoprazol/administração & dosagem , Obesidade Infantil/genética , Inibidores da Bomba de Prótons/farmacocinética , Inibidores da Bomba de Prótons/administração & dosagemRESUMO
BACKGROUND: Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear. METHODS: In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted secondary outcomes included ventilator-associated pneumonia, Clostridioides difficile infection, and patient-important bleeding. RESULTS: A total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P = 0.25). Patient-important bleeding was reduced with pantoprazole; all other secondary outcomes were similar in the two groups. CONCLUSIONS: Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.).
Assuntos
Estado Terminal , Pantoprazol , Inibidores da Bomba de Prótons , Respiração Artificial , Humanos , Pantoprazol/uso terapêutico , Pantoprazol/efeitos adversos , Pantoprazol/administração & dosagem , Respiração Artificial/efeitos adversos , Masculino , Pessoa de Meia-Idade , Feminino , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/administração & dosagem , Idoso , Hemorragia Gastrointestinal/prevenção & controle , 2-Piridinilmetilsulfinilbenzimidazóis/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis/efeitos adversos , 2-Piridinilmetilsulfinilbenzimidazóis/administração & dosagem , Úlcera Péptica/prevenção & controle , Unidades de Terapia Intensiva , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Método Duplo-Cego , Estresse Fisiológico , AdultoRESUMO
Abomasal ulcers are recognized in sheep of all ages, but research regarding therapeutic interventions is limited. Proton Pump Inhibitors (PPIs) such as pantoprazole, are clinically used with a paucity of evidence regarding efficacy in mature sheep. Intravenous and subcutaneously administered pantoprazole dosed at 1.0 mg/kg in adult sheep will increase the pH of abomasal fluid compared to pre-administration baseline. The objectives were to assess the effect of pantoprazole, after single and multiple administration, on abomasal fluid pH in adult sheep. A third objective was to describe the pharmacokinetic parameters of IV and SC pantoprazole. Four clinically healthy adult Southdown ewes previously fitted with a gastrostomy tube in the abomasum were utilized in this randomized, 2-way cross-over trial. Ewes received pantoprazole (1.0 mg/kg) as a single and 3-dose regimen (every 24 hours). After a 10 day washout period the reverse treatment was applied. Blood for analysis of pantoprazole concentration was collected intermittently for 24 hours, and abomasal fluid pH was measured at intervals for a 96-hour period. The pH of the abomasal fluid was higher in pantoprazole treatments for up to 24 hours after dosing. Following intravenous administration of pantoprazole to study ewes, elimination half-life, volume of distribution, and clearance of pantoprazole was estimated as 3.29 hours, 0.35 L/kg, and 65.26 mL/hr/kg respectively. After subcutaneous dosing, maximum concentration, time to maximum concentration, half-life of elimination, and volume of distribution, were estimated as 2604 ng/mL, 0.55 hours, 2.48 hours, and 0.37 L/kg. Additionally, the bioavailability was estimated as 83.33%. Pantoprazole administered IV or SC may be useful for treatment or prevention of abomasal ulcers in adult sheep.
Assuntos
Pantoprazol , Animais , Pantoprazol/farmacocinética , Pantoprazol/administração & dosagem , Ovinos , Feminino , Injeções Subcutâneas , Concentração de Íons de Hidrogênio , Inibidores da Bomba de Prótons/farmacocinética , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/farmacologia , Abomaso/efeitos dos fármacos , Administração Intravenosa , Estudos Cross-Over , Injeções IntravenosasRESUMO
Abomasal ulcers are a significant concern in intensive animal farming due to their impact on animal health and productivity. While proton pump inhibitors (PPIs) such as pantoprazole (PTZ) show promise in treating these ulcers, data on PTZ's pharmacokinetics (PK) in adult goats and sheep are limited. This study aims to fill this gap by investigating and comparing PTZ's PK in these species following single intravenous (IV) and subcutaneous (SC) administrations. Five healthy male goats and sheep were included in the study. PTZ concentrations in plasma samples were determined using a validated analytical method. Non-compartmental analysis was conducted, and statistical comparisons were made between IV and SC administrations and between species. Sheep and goats showed similar systemic exposure levels regardless of the administration route. However, sheep had a shorter t1/2 due to a higher Vd compared to goats. Cl values were comparable in both species, with low extraction ratio values. There were no significant differences in Cmax and Tmax between the two species with regards to SC administration, and complete bioavailability was observed. The MAT exceeded the t1/2 in both species, indicating a potential flip-flop phenomenon. Considering the AUC as a predictor for drug efficacy, and observing no significant differences in systemic exposure between sheep and goats for any route of administration, dosage adjustment between the two species may not be necessary. In field settings, SC administration proves more practical, providing not only complete bioavailability but also a longer half-life compared to IV. Further studies are warranted to explore the PK/PD of PTZ in small ruminants with abomasal ulcers, to fully comprehend its therapeutic efficacy in such scenarios.
Assuntos
Cabras , Pantoprazol , Animais , Masculino , Ovinos , Pantoprazol/farmacocinética , Pantoprazol/administração & dosagem , Injeções Subcutâneas/veterinária , Injeções Intravenosas/veterinária , Inibidores da Bomba de Prótons/farmacocinética , Inibidores da Bomba de Prótons/administração & dosagem , Área Sob a Curva , Disponibilidade Biológica , Meia-VidaRESUMO
A drug-resin liquid delayed-release suspension of pantoprazole sodium (PAZ-Na) was prepared to improve the effectiveness, convenience and safety of peptic ulcer treatment in children, the elderly and patients with dysphagia. Pantoprazole sodium drug-resin complexes (PAZ-Na-DRC) were prepared using the bath method. The fluidized bed coating method is used to coat it and then add excipients to make a dry suspension prepared before use. The parameters of the in vitro release experimental conditions were optimized and the drug release curve showed delayed release. Rats were given commercial PAZ-Na enteric-coated pellet capsules and the PAZ-Na delayed release suspension via intragastric administration. The results showed that the Tmax of the PAZ-Na delayed release suspension was increased from 2h to 4h compared with the PAZ-Na enteric-coated pellet capsules. Similarly, the Cmax was reduced from 6.162µg/mL to 3.244µg/mL with the concentration-time curve is very gentle compared with the commercial drug capsules. After oral administration, the relative bioavailability of PAZ-Na delayed release suspension (AUC0-24 of 19.578 µgâ¢hâ¢mL-1) compared with the commercial drug (AUC0-24 of 17.388 µgâ¢hâ¢mL-1) was 112.67%. The findings showed that the PAZ-Na delayed release suspension for oral administration was successfully formulated with highly improved pharmacokinetic indices.
Assuntos
Preparações de Ação Retardada , Pantoprazol , Suspensões , Pantoprazol/farmacocinética , Pantoprazol/administração & dosagem , Animais , Masculino , Ratos , Liberação Controlada de Fármacos , Disponibilidade Biológica , Administração Oral , Composição de Medicamentos , Excipientes/química , Ratos Sprague-DawleyRESUMO
BACKGROUND: Long-term use of proton pump inhibitors (PPIs) has been linked to an increased risk of osteoporosis, with various indirect mechanisms so far identified. Although no direct underlying mechanism for effect on bone cells have been investigated with the use of PPIs. Melastatin-like transient receptor potential 7 (TRPM7)channel has been engaged in the proliferation of bone cells. TRPM7 channel is regulated by extracellular Mg2+ and Ca2+ level, that further encourages to analyse if any imbalance with pantoprazole usage could alter bone remodelling process mediated by TRPM7. OBJECTIVES: The present study was conducted to investigate the effect of pantoprazole on the calcium and magnesium level, the cations involved in the bone remodelling process, as well as role of the TRPM7 channel in the proliferation of bone cells. METHODS: A cytotoxicity study was carried out to study the effect of pantoprazole on the bone cell using MC3T3-E1 cell line, together with the expression of TRPM7 was determined post-pantoprazole treatment. An in vivo study in rats was carried out for estimation of Ca2+, Mg2+ and Ca2+/Mg2+ ratio as well as bone strength was measured over a duration of 4 weeks and 8 weeks with the treatment of pantoprazole. A pilot-scale clinical study was carried out in patients with a fracture to support the evidence of preliminary findings from in-vitro and in vivo studies. RESULTS: MC3T3-E1 cell line treated with pantoprazole showed decreased cell viability in a dose-dependent manner and reduced expression of TRPM7 channel, evidencing interaction of TRPM7 and pantoprazole in the bone remodelling process. A pilot study conducted on 12 patients having major fractures showed changes in serum Mg2+ and Ca2+ levels over a period of 1 month as well as the animal study also showed ionic imbalance over 8-week treatment with pantoprazole. Bone density measured for the patient at the end of the 1-month treatment was found to be in the osteopenic category, together with the animal study which showed a decrease in femur bone strength for the animal treated with pantoprazole over a period of 8 weeks. CONCLUSION: The study findings proved a negative impact of pantoprazole use on Ca2+ and Mg2+ levels, which can impact TRPM7-mediated bone remodelling which serves to be a possible mechanism for osteoporosis upon pantoprazole use.
Assuntos
Osso e Ossos/efeitos dos fármacos , Pantoprazol/farmacologia , Inibidores da Bomba de Prótons/farmacologia , Canais de Cátion TRPM/efeitos dos fármacos , Animais , Densidade Óssea , Cálcio/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Magnésio/metabolismo , Masculino , Pantoprazol/administração & dosagem , Projetos Piloto , Estudos Prospectivos , Inibidores da Bomba de Prótons/administração & dosagem , Ratos , Ratos WistarRESUMO
This study aimed to evaluate the bioequivalence of 2 pantoprazole sodium enteric-coated tablet formulations, a generic formulation and a branded formulation, and to investigate their pharmacokinetic and safety profiles. The study was designed as a single-center, randomized, open-label, single-dose, dual-period, and 2-sequence crossover trial, and was divided into fasting and postprandial human bioequivalence trials. In the first trial, 36 subjects were fasted overnight before they were given generic or branded tablets (during 2 separate administration periods). Separately, 42 subjects were provided a high-fat meal 1 hour before the drugs were administered. Blood specimens of each subject were obtained up to 24 hours after drug administration. No significant differences were observed between the pharmacokinetic profiles of the generic and branded pantoprazole sodium enteric-coated tablets. Bioequivalence was evaluated using 90% confidence intervals for the ratio of test/reference log area under the concentration-time curve over 24 hours, log area under the concentration-time curve to infinity (AUC0-∞ ), and log peak concentration (Cmax ). The 90% confidence intervals of the least squares geometric mean ratio of Cmax , area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t ), and AUC0-∞ of 36 subjects in the fasting trial and of 40 of 41 subjects in the postprandial trial (Cmax [41], AUC0-t [41], and AUC0-∞ [40]) were in accordance with the bioequivalence criteria. No severe adverse effects were detected. The generic and branded pantoprazole sodium enteric-coated tablets were considered bioequivalent with similar safety profiles.
Assuntos
Medicamentos Genéricos/administração & dosagem , Pantoprazol/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Área Sob a Curva , Estudos Cross-Over , Medicamentos Genéricos/efeitos adversos , Medicamentos Genéricos/farmacocinética , Jejum , Feminino , Interações Alimento-Droga , Humanos , Masculino , Pantoprazol/efeitos adversos , Pantoprazol/farmacocinética , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/farmacocinética , Comprimidos com Revestimento Entérico , Equivalência Terapêutica , Adulto JovemAssuntos
Anti-Helmínticos/administração & dosagem , Obstrução da Saída Gástrica/diagnóstico , Pantoprazol/administração & dosagem , Praziquantel/administração & dosagem , Taenia/isolamento & purificação , Teníase/parasitologia , Dor Abdominal/tratamento farmacológico , Dor Abdominal/parasitologia , Adulto , Animais , Etiópia , Obstrução da Saída Gástrica/parasitologia , Gastroscopia , Humanos , Masculino , Teníase/tratamento farmacológico , Vômito/tratamento farmacológico , Vômito/parasitologiaRESUMO
The carrot plant (Daucus carota) and its components are traditionally reported for the management of gastric ulcers. This study was performed to evaluate the role of carrot when administered concurrently with a conventional antiulcer treatment, pantoprazole, in alleviating gastric and duodenal ulcers in female experimental animals. The study involved standard animal models to determine the ulcer preventive effect using pylorus ligation, ethanol, and stress induced acute gastric ulcer models and duodenal ulcer models involving cysteamine. Acetic acid-induced chronic gastric ulcer and indomethacin-induced gastric ulcer models were used to evaluate the ulcer healing effect. Carrot fruit (500 mg/kg) and its co-administration with pantoprazole produced significant protection in an ethanol- and stress-induced acute gastric ulcer and cysteamine-induced duodenal ulcer. The healing of the acetic acid-induced chronic gastric ulcer was also augmented with this combination. Both total proteins and mucin contents were significantly increased in indomethacin-induced gastric ulcers. Similarly, in pylorus ligation, the pepsin content of gastric juice, total acidity, and free acidity were reduced. Overall, both ulcer preventive effects and ulcer healing properties of the pantoprazole were significantly enhanced in animals who received the co-administration of carrot fruit (500 mg/kg).
Assuntos
Antiulcerosos/administração & dosagem , Daucus carota/química , Indometacina/efeitos adversos , Pantoprazol/administração & dosagem , Preparações de Plantas/administração & dosagem , Piloro/efeitos dos fármacos , Ácido Acético/química , Animais , Antioxidantes/farmacologia , Compostos de Bifenilo/química , Cisteamina/química , Sinergismo Farmacológico , Etanol/química , Feminino , Sequestradores de Radicais Livres/química , Concentração Inibidora 50 , Pepsina A/química , Picratos/química , Ratos , Ratos WistarRESUMO
BACKGROUND/AIM: Proton pump inhibitor (PPI) alone is not satisfactory for the treatment of gastroesophageal reflux disease (GERD). Therefore, we investigated the efficacy of DA-5204 (Stillen 2X, 90âmg of Artemisia asiatica 95% ethanol extract per tablet) and PPI combination therapy on GERD in comparison to PPI alone. METHODS: This randomized, double-blind, placebo-controlled study randomly assigned 70 patients with endoscopically proven esophageal mucosal injury (Los Angeles classification grade A or B) into 2 groups: pantoprazole 40âmg once daily with DA-5204 twice daily (DA-5204 group) or pantoprazole 40âmg once daily with placebo twice daily (placebo group) for 4 weeks. The primary endpoint was endoscopic healing rate. The secondary endpoint was sufficient relief (≥50% reduction) of symptoms using GERD Questionnaire. RESULTS: Final analyses included 29 patients with the DA-5204 group and 30 patients with the placebo group. At weeks 4, there was no significant difference in the endoscopic healing rate between the 2 groups (DA-5204 vs placebo; 96.6% vs 93.3%; P = 1.000). However, the rate of residual minimal change was significantly lower in the DA-5204 group (5/28, 17.9%) than in the placebo group (17/28, 60.7%) (Pâ<â.001). The rates of symptom relief were not different between the DA-5204 group and the placebo group (all Pâ>â.05). CONCLUSION: Combined therapy with PPI and DA-5204 has no additional effect on the endoscopic healing rate compared to PPI alone. However, it may be beneficial in resolving minimal change.
Assuntos
Artemisia , Esofagite/tratamento farmacológico , Refluxo Gastroesofágico/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Idoso , Método Duplo-Cego , Quimioterapia Combinada , Endoscopia do Sistema Digestório , Esofagite/etiologia , Feminino , Refluxo Gastroesofágico/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Pantoprazol/administração & dosagem , Projetos Piloto , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: Fedratinib, an oral, selective Janus kinase 2 inhibitor with activity against both wild-type and mutant Janus kinase 2, has pH-dependent solubility, with free solubility at pH 1. Concomitant administration of drugs that reduce gastric acid secretion, such as pantoprazole, may decrease the absorption of fedratinib and affect patient outcomes. The aim of this study was to evaluate the impact of 7-day repeated 40-mg doses of pantoprazole on the pharmacokinetic (PK) properties of a single 500-mg dose of fedratinib in healthy male subjects. METHODS: In this phase I, single-center, open-label, two-period, two-treatment, fixed-sequence crossover study, healthy male subjects were administered a single dose of fedratinib 500 mg on day 1 in Period 1, followed by pantoprazole 40 mg daily for 7 days (day 1 to day 7) and a single dose of fedratinib 500 mg on day 7 in Period 2. After the discontinuation of nine subjects due to vomiting, the protocol was amended to provide ondansetron as antiemetic prophylaxis to an additional ten enrolled subjects. RESULTS: Twenty-six subjects were included. Repeated doses of pantoprazole 40 mg resulted in clinically insignificant increases in fedratinib exposure. Maximum plasma concentration increased by 1.09-fold and area under the plasma concentration-time curve from time 0 to infinity increased by 1.15-fold. All treatment-emergent adverse events were mild or moderate, except for one instance of neutropenia, which was considered unrelated to study intervention. CONCLUSION: Coadministration with pantoprazole did not have clinically meaningful effects on fedratinib PK. No new or unexpected safety signals were observed with fedratinib.
Assuntos
Interações Medicamentosas , Janus Quinase 2/antagonistas & inibidores , Pantoprazol , Pirrolidinas , Sulfonamidas , Adulto , Disponibilidade Biológica , Estudos Cross-Over , Monitoramento de Medicamentos/métodos , Quimioterapia Combinada , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/farmacocinética , Voluntários Saudáveis , Humanos , Masculino , Pantoprazol/administração & dosagem , Pantoprazol/efeitos adversos , Pantoprazol/farmacocinética , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/farmacocinética , Pirrolidinas/administração & dosagem , Pirrolidinas/efeitos adversos , Pirrolidinas/farmacocinética , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Sulfonamidas/farmacocinética , Resultado do TratamentoRESUMO
BACKGROUND: Upper gastrointestinal (GI) ulceration and bleeding in critically ill dogs can cause severe anemia and increase morbidity. Acid suppressants using proton pump inhibitors or histamine-2 receptor blockers administered IV is commonly recommended. HYPOTHESIS/OBJECTIVES: To evaluate the efficacy of IV administered esomeprazole, pantoprazole, and famotidine constant rate infusion (CRI) on increasing the intragastric pH of dogs. We hypothesized that esomeprazole and famotidine CRI would provide superior acid suppression compared to pantoprazole and reach pH goals for the treatment of GI bleeding. ANIMALS: Nine healthy research Beagles. METHODS: Randomized, 3-way crossover. Dogs received pantoprazole or esomeprazole at 1 mg/kg IV q12h and famotidine with a loading dose of 1 mg/kg followed by 8 mg/kg IV CRI daily for 3 consecutive days. The intragastric pH was recorded at baseline and for 72 hours of treatment. The mean pH and the mean percentage time (MPT) the intragastric pH was ≥3 or ≥4 were compared among and within treatment groups. RESULTS: Significant increases in mean pH (P < 0.0001), MPT ≥3 (P < 0.001), and MPT ≥4 (P = 0.0006) were noted over time with all 3 treatments. The time effect did not differ by treatment for mean pH, MPT ≥3, and MPT ≥4 (P = .29, .56, and .37, respectively); however, only esomeprazole and famotidine CRI achieved the goals established for the treatment of gastroduodenal ulceration in people. CONCLUSIONS AND CLINICAL IMPORTANCE: Famotidine CRI and esomeprazole might be superior acid suppressants compared to standard doses of pantoprazole for the first 72 hours of treatment.
Assuntos
Esomeprazol/farmacologia , Famotidina/farmacologia , Pantoprazol/farmacologia , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/uso terapêutico , Estudos Cross-Over , Cães , Esomeprazol/administração & dosagem , Famotidina/administração & dosagem , Feminino , Concentração de Íons de Hidrogênio , Injeções Intravenosas , Masculino , Pantoprazol/administração & dosagemRESUMO
Side effects of proton pump inhibitors (PPI) can be linked to the changes in the intestinal microbiome that occur during therapy, especially in long-term users. Therefore, the microbiome might also be a key player in the reduction of PPI side effects. We tested the effects of a three-month intervention with a multispecies synbiotic on intestinal inflammation, gut barrier function, microbiome composition, routine laboratory parameters and quality of life in patients with long-term PPI therapy. Thirty-six patients received a daily dose of a multispecies synbiotic for three months and were clinically observed without intervention for another three months. After intervention 17% of patients reached normal calprotectin levels; the overall reduction did not reach statistical significance (-18.8 ng/mg; 95%CI: -50.5; 12.9, p = 0.2). Elevated zonulin levels could be significantly reduced (-46.3 ng/mg; 95%CI: -71.4; -21.2; p < 0.001). The abundance of Stomatobaculum in the microbiome was reduced and Bacillus increased during the intervention. Furthermore, albumin, alkaline phosphatase and thrombocyte count were significantly increased and aspartate transaminase was significantly decreased during intervention. Gastrointestinal quality of life showed significant improvements. In conclusion, microbiome-related side effects of long-term PPI use can be substantially reduced by synbiotic intervention. Further studies are warranted to optimize dosage and duration of the intervention.
Assuntos
Antiulcerosos/efeitos adversos , Disbiose/prevenção & controle , Refluxo Gastroesofágico/terapia , Úlcera Péptica/terapia , Prebióticos/administração & dosagem , Probióticos/uso terapêutico , Inibidores da Bomba de Prótons/efeitos adversos , Idoso , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Antiulcerosos/administração & dosagem , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Bacillus/classificação , Bacillus/isolamento & purificação , Clostridiales/classificação , Clostridiales/isolamento & purificação , Disbiose/induzido quimicamente , Disbiose/fisiopatologia , Esomeprazol/administração & dosagem , Esomeprazol/efeitos adversos , Feminino , Refluxo Gastroesofágico/microbiologia , Refluxo Gastroesofágico/fisiopatologia , Microbioma Gastrointestinal/fisiologia , Regulação da Expressão Gênica , Haptoglobinas/genética , Haptoglobinas/metabolismo , Humanos , Lactobacillus/classificação , Lactobacillus/isolamento & purificação , Lactococcus/classificação , Lactococcus/isolamento & purificação , Complexo Antígeno L1 Leucocitário/genética , Complexo Antígeno L1 Leucocitário/metabolismo , Masculino , Pessoa de Meia-Idade , Pantoprazol/administração & dosagem , Pantoprazol/efeitos adversos , Úlcera Péptica/microbiologia , Úlcera Péptica/fisiopatologia , Projetos Piloto , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Inibidores da Bomba de Prótons/administração & dosagem , Qualidade de VidaRESUMO
BACKGROUND: Several studies demonstrated that proton pump inhibitors (PPIs) co-administrated with dabigatran in patients with atrial fibrillation (AF) decreased dabigatran trough and peak plasma levels. However, it is still unknown whether this interaction is reversible or not, and whether the withdrawal of PPI would lead to normalization of dabigatran plasma levels. AIM OF STUDY: The aim of this study was to determine the effect of PPI withdrawal on dabigatran plasma levels in patients with AF. METHODS: This pilot prospective study enrolled 23 AF patients on long-term dabigatran and PPI therapy (omeprazole 20 mg twice daily or pantoprazole 40 mg once daily). Dabigatran trough and peak levels (ng/mL) were tested on PPI and after a 2-week period of PPI withdrawal with Hemoclot Thrombin Inhibitor Assay. RESULTS: The analysis of dabigatran plasma levels demonstrated significant elevation in trough dabigatran levels after 2 weeks of PPI withdrawal (97.2 ± 79.7 vs. 163.8 ± 105.5 ng/mL; P < 0.05). Moreover, significantly higher peak dabigatran levels were observed after 2 weeks of PPI withdrawal (142.4 ± 102.8 vs. 255 ± 129.5 ng/mL; P ≤ 0.001). CONCLUSIONS: This study showed that a 2-week period of PPI withdrawal lead to a significant increase in dabigatran trough and peak plasma levels in patients with AF.
Assuntos
Antitrombinas/sangue , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/sangue , Omeprazol/administração & dosagem , Pantoprazol/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antitrombinas/administração & dosagem , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico , Dabigatrana/administração & dosagem , Esquema de Medicação , Interações Medicamentosas , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Omeprazol/efeitos adversos , Pantoprazol/efeitos adversos , Projetos Piloto , Estudos Prospectivos , Inibidores da Bomba de Prótons/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
The current study was undertaken to evaluate the effect of combined therapy of gabapentin and pantoprazole against forestomach and pylorus ligation-induced gastric esophageal reflux disease (GERD) in albino Wistar rats. Rats were randomly divided into five groups, each group consisting of six rats, fasted for 24 h, underwent forestomach and pylorus ligation, received normal saline (3 ml/kg, p.o.), normal control, toxic control, pantoprazole (30 mg/kg, p.o.), gabapentin (50 mg/kg, p.o.), or their combination. After 10 h, animals were killed by cervical dislocation and evaluated for pH of gastric content, volume of gastric juice, total acidity, and esophagitis index. Esophageal tissues were further analyzed for biochemical parameters such as superoxide dismutase, glutathione, catalase, thiobarbituric acid reactive substances, and protein carbonyl, and scanning electron microscopy (SEM) and histopathology were used for morphological evaluation. The results show the combination therapy of gabapentin and pantoprazole significantly inhibited the volume of gastric juice and total acidity esophagitis index and significantly increased the pH of gastric juice. Treatment with gabapentin and pantoprazole exhibited maximum antioxidant effect in comparison with monotherapy. Marked protection and restoration of normal morphology was observed through SEM and histopathology in the combination therapy as compared to monotherapy. Finally, it was concluded that combination therapy of pantoprazole and gabapentin has beneficial effect against GERD.
Assuntos
Gabapentina/uso terapêutico , Refluxo Gastroesofágico/prevenção & controle , Pantoprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Estômago/efeitos dos fármacos , Vias Aferentes/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Quimioterapia Combinada , Gabapentina/administração & dosagem , Esvaziamento Gástrico/efeitos dos fármacos , Refluxo Gastroesofágico/patologia , Pantoprazol/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Ratos Wistar , Estômago/inervação , Estômago/patologiaRESUMO
Agenesis of the dorsal pancreas is a rare congenital pancreatic malformation. We herein describe a 67-year-old woman with a 5-day history of lower back pain who was eventually diagnosed with agenesis of the dorsal pancreas. Abdominal computed tomography showed an enlarged pancreatic head, but the pancreatic body and tail were invisible. The magnetic resonance imaging findings were similar to the computed tomography findings. Magnetic resonance cholangiopancreatography showed that the major pancreatic duct was mildly dilated but otherwise normal. Endoscopic ultrasound revealed absence of the pancreatic body and tail, an enlarged head of the pancreas, and mild pancreatic duct dilation. The final diagnosis was dorsal pancreatic agenesis.
Assuntos
Anormalidades Congênitas/diagnóstico por imagem , Endossonografia , Dor Lombar/etiologia , Pâncreas/anormalidades , Idoso , Alprostadil/administração & dosagem , Colangiopancreatografia por Ressonância Magnética , Terapia de Reposição de Enzimas , Feminino , Humanos , Dor Lombar/tratamento farmacológico , Pâncreas/diagnóstico por imagem , Pantoprazol/administração & dosagem , Tomografia Computadorizada por Raios XRESUMO
The optimization of the coating process for minitablets is extremely important in fluidized bed systems, and allows knowledge acquisition about the process for modern multiparticulate forms. The coating of minitablets allows the development of modified-release pediatric drugs. In our study, 3-mm minitablets with pantoprazole were coated to obtain an enteric product. The experiments were designed to evaluate the quality of the enteric product by efficiency and quality of film coating. Four process parameters at two levels were examined, and 16 experiments for two different fluid bed systems in laboratory-scale batches were performed. During analysis, the critical parameters of inlet airflow rate (X1) and coating mixture flow rate (X3) in different fluid bed coaters were examined. The findings indicate that apparatus construction has a significant effect on the different process parameters. Despite the fact that statistical analysis is directly related to the tested conditions, it creates opportunity to anticipate certain problems while scaling up, and a possibility to minimize them.
Assuntos
Excipientes/química , Pantoprazol/administração & dosagem , Tecnologia Farmacêutica , Preparações de Ação Retardada , Pantoprazol/química , Comprimidos , Comprimidos com Revestimento EntéricoRESUMO
Introduction: Limitations of urine drug-screening (UDS) by immunoassay include false-positive results. Pantoprazole, a proton-pump inhibitor (PPI), is reported to cause false-positive results for THC on UDS. The objective of this study was to determine if oral PPIs cause false-positive THC results using the THC One Step Marijuana Test Strip®.Methods: Eligible healthy volunteers completed a 5-day course of a PPI followed by urine testing using the THC One Step Marijuana Test Strip®. Phase one included 3 subjects taking pantoprazole 40 mg once daily for 5 days. On day 5, urine specimens underwent THC screening. Phase two included 9 subjects randomized to 5-day supply of once-daily oral esomeprazole 20 mg, lansoprazole 15 mg, or omeprazole 20 mg. All study methods and testing mirrored those in phase one.Results: All 12 subjects completed the study protocol. All urine samples collected on day 5 were negative for THC in all subjects.Discussion: Our results demonstrate that oral PPIs did not cause a false-positive THC using the THC One Step Marijuana Test Strip®. Limitations include small sample size, use of a single commercial immunoassay, and inability to confirm medication compliance. Further, large-scale research using other commercial urine immunoassays is warranted.
Assuntos
Dronabinol/urina , Pantoprazol/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Detecção do Abuso de Substâncias/métodos , Administração Oral , Interações Medicamentosas , Reações Falso-Positivas , Voluntários Saudáveis , Humanos , Imunoensaio , Detecção do Abuso de Substâncias/normasRESUMO
Upper gastrointestinal bleeding (UGIB) is a common life-threatening presentation in the emergency department. Causes are typically divided into variceal and non-variceal bleeds. Non-variceal pathologies typically include bleeding peptic ulcers, haemorrhagic gastritis and Mallory Weiss Tears. Occassionally, less common pathologies are encountered such as Dieulafoy's lesions, haemosuccus pancreas, haemobilia or aorto-enteric fistula. The following report documents the case of a 49-year-old man who presented with an UGIB. His risk factors included a history of nonsteroidal anti-inflammatory drug, smoking and ethanol abuse. Despite his typical presentation and risk factors, investigation revealed an unusual and rare pathology. He was found to have a giant splenic artery aneurysm, abutting and eroding the gastric mucosa. Diagnosis was made using a combination of gastro-oesophagoscopy and CT scan. Successful treatment consisted of angio-embolisation of the aneurysm.