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1.
Cancer Epidemiol Biomarkers Prev ; 30(12): 2302-2308, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34620629

RESUMEN

BACKGROUND: The discovery that ranitidine is contaminated with N-nitrosodimethylamine, a suspected human carcinogen, raises the hypothesis of a gastrointestinal carcinogenic effect; however, evidence remains inconclusive. METHODS: We used the nationwide Danish Prescription Registry to identify a cohort of incident ranitidine users and two active comparator cohorts comprising users of other histamine-2 receptor blockers (H2RB) and users of proton pump inhibitors (PPI). All Danish adults with a first prescription of ranitidine, other H2RBs, or PPIs in 1996 through 2008 were followed virtually completely through 2018 for incidence of esophageal, stomach, liver, and pancreatic cancers. We used Cox regression with propensity-score weighting to calculate hazard ratios and 10-year cumulative risk with 95% confidence intervals. RESULTS: We ascertained 276 newly diagnosed esophageal, 342 stomach, 133 hepatocellular, and 517 pancreatic cancers among ranitidine users during follow-up (median 14 years). In comparison with use of other H2RBs or PPIs, we found no consistent evidence of increased HRs or excess 10-year cumulative risk of any upper gastrointestinal cancer following ranitidine use. We observed no association after restriction to subjects with at least 5 or 10 prescriptions or those with 10 prescriptions and at least 10 years of follow-up. CONCLUSIONS: Our large prospective study using high-quality prescription and cancer incidence data, with two active comparator groups, provides no compelling evidence that ranitidine increases the risk of upper gastrointestinal cancers. IMPACT: Our results, which do not support any carcinogenic effect on esophagus, stomach, liver or pancreas, should be reassuring for millions of concerned past users of ranitidine.


Asunto(s)
Neoplasias Gastrointestinales/inducido químicamente , Antagonistas de los Receptores H2 de la Histamina/efectos adversos , Ranitidina/efectos adversos , Adulto , Estudios de Casos y Controles , Dinamarca , Dimetilnitrosamina/envenenamiento , Femenino , Antagonistas de los Receptores H2 de la Histamina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Ranitidina/administración & dosificación , Sistema de Registros
2.
JAMA ; 326(3): 240-249, 2021 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-34180947

RESUMEN

Importance: In 2019, the US Food and Drug Administration (FDA) received a citizen petition indicating that ranitidine contained the probable human carcinogen N-nitrosodimethylamine (NDMA). In addition, the petitioner proposed that ranitidine could convert to NDMA in humans; however, this was primarily based on a small clinical study that detected an increase in urinary excretion of NDMA after oral ranitidine consumption. Objective: To evaluate the 24-hour urinary excretion of NDMA after oral administration of ranitidine compared with placebo. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled, crossover clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) conducted in 18 healthy participants. The study began in June 2020, and the end of participant follow-up was July 1, 2020. Interventions: Participants were randomized to 1 of 4 treatment sequences and over 4 periods received ranitidine (300 mg) and placebo (randomized order) with a noncured-meats diet and then a cured-meats diet. The cured-meats diet was designed to have higher nitrites, nitrates (nitrate-reducing bacteria can convert nitrates to nitrites), and NDMA. Main Outcome and Measure: Twenty-four-hour urinary excretion of NDMA. Results: Among 18 randomized participants (median age, 33.0 [interquartile range {IQR}, 28.3 to 42.8] years; 9 women [50%]; 7 White [39%], 11 African American [61%]; and 3 Hispanic or Latino ethnicity [17%]), 17 (94%) completed the trial. The median 24-hour NDMA urinary excretion values for ranitidine and placebo were 0.6 ng (IQR, 0 to 29.7) and 10.5 ng (IQR, 0 to 17.8), respectively, with a noncured-meats diet and 11.9 ng (IQR, 5.6 to 48.6) and 23.4 ng (IQR, 8.6 to 36.7), respectively, with a cured-meats diet. There was no statistically significant difference between ranitidine and placebo in 24-hour urinary excretion of NDMA with a noncured-meats diet (median of the paired differences, 0 [IQR, -6.9 to 0] ng; P = .54) or a cured-meats diet (median of the paired differences, -1.1 [IQR, -9.1 to 11.5] ng; P = .71). No drug-related serious adverse events were reported. Conclusions and Relevance: In this trial that included 18 healthy participants, oral ranitidine (300 mg), compared with placebo, did not significantly increase 24-hour urinary excretion of NDMA when participants consumed noncured-meats or cured-meats diets. The findings do not support that ranitidine is converted to NDMA in a general, healthy population. Trial Registration: ClinicalTrials.gov Identifier: NCT04397445.


Asunto(s)
Dimetilnitrosamina/orina , Antagonistas de los Receptores H2 de la Histamina/farmacocinética , Ranitidina/farmacocinética , Administración Oral , Adulto , Estudios Cruzados , Método Doble Ciego , Femenino , Antagonistas de los Receptores H2 de la Histamina/administración & dosificación , Humanos , Masculino , Placebos/farmacocinética , Ranitidina/administración & dosificación
3.
Br J Cancer ; 124(10): 1647-1652, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33762718

RESUMEN

BACKGROUND: Ranitidine, a histamine 2 blocker, is the standard of care to prevent hypersensitivity reactions (HSRs) caused by paclitaxel infusion. However, the added value of ranitidine in this premedication regimen is controversial. Therefore, we compared the incidence of HSRs during paclitaxel treatment between a standard regimen including ranitidine and a regimen without ranitidine. METHODS: This prospective, pre-post interventional, non-inferiority study compared the standard premedication regimen (N = 183) with dexamethasone, clemastine and ranitidine with a premedication regimen without ranitidine (N = 183). The primary outcome was the incidence of HSR grade ≥3. Non-inferiority was determined by checking whether the upper bound of the two-sided 90% confidence interval (CI) for the difference in HSR rates excluded the +6% non-inferiority margin. RESULTS: In both the pre-intervention (with ranitidine) and post-intervention (without ranitidine) group 183 patients were included. The incidence of HSR grade ≥3 was 4.4% (N = 8) in the pre-intervention group and 1.6% (N = 3) in the post-intervention group: difference -2.7% (90% CI: -6.2 to 0.1). CONCLUSIONS: As the upper boundary of the 90% CI does not exceed the predefined non-inferiority margin of +6%, it can be concluded that a premedication regimen without ranitidine is non-inferior to a premedication regimen with ranitidine. CLINICAL TRIAL REGISTRATION: www.trialregister.nl ; NL8173.


Asunto(s)
Hipersensibilidad a las Drogas/prevención & control , Neoplasias/tratamiento farmacológico , Paclitaxel/efectos adversos , Premedicación/métodos , Ranitidina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Quimioprevención/efectos adversos , Quimioprevención/métodos , Clemastina/administración & dosificación , Dexametasona/administración & dosificación , Hipersensibilidad a las Drogas/epidemiología , Hipersensibilidad a las Drogas/patología , Quimioterapia Combinada , Estudios de Equivalencia como Asunto , Femenino , Antagonistas de los Receptores H2 de la Histamina/administración & dosificación , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Humanos , Infusiones Intravenosas , Masculino , Inutilidad Médica , Persona de Mediana Edad , Neoplasias/epidemiología , Neoplasias/patología , Países Bajos/epidemiología , Paclitaxel/administración & dosificación , Premedicación/efectos adversos , Ranitidina/administración & dosificación , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
5.
Drug Dev Ind Pharm ; 45(2): 231-243, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30260710

RESUMEN

OBJECTIVE: Oral gastroretentive system is one of the site-specific drug delivery system, which is designed to be retained in upper GIT for a prolonged time. Ranitidine hydrochloride (RHCl), which is used frequently in treatment of peptic ulcer, is a suitable candidate for gastroretentive delivery systems. Dependently, floating oil-entrapped alginate beads of RHCl were developed and evaluated as an approach to site-specific delivery avoiding colonic degradation and enhancing both bioavailability and the proposed local effect. METHODS: Different formulations of floating beads were suggested and randomized using 24 full factorial design. Optimized formulation was subjected for in vivo studies to measure the oral bioavailability and the healing effect of induced peptic ulcers. RESULTS: Beads size ranged from 1.32 to 2.3 mm. All beads revealed excellent floating capabilities. Optimum formulation (F12) has entrapment efficiency of 70%, drug loading of 7% and 71% RHCl released after 6 h. SEM of F12 shows a grossly spherical structure with presence of oil droplets distributed throughout structure. AUC obtained from F12 was nonsignificantly higher than that of a commercial tablet. Signs of ulcer healing appeared clearly with F12 through appearance of granulation tissue, collagen fibers and newly formed blood vessels. Healing rate and extent obtained with a commercial tablet were less than F12. Quantitative analysis confirmed histopathological findings. CONCLUSION: Floating oil-entrapped beads are a promising approach for RHCl delivery to remain in stomach for a longer time ensuring site-specific delivery and consequently, enhancing local healing effect of peptic ulcers.


Asunto(s)
Antiulcerosos/administración & dosificación , Antiulcerosos/uso terapéutico , Aceites/química , Úlcera Péptica/tratamiento farmacológico , Ranitidina/administración & dosificación , Ranitidina/uso terapéutico , Animales , Antiulcerosos/farmacocinética , Disponibilidad Biológica , Colágeno/metabolismo , Composición de Medicamentos , Sistemas de Liberación de Medicamentos , Excipientes/química , Tejido de Granulación/patología , Masculino , Neovascularización Fisiológica/efectos de los fármacos , Tamaño de la Partícula , Úlcera Péptica/patología , Conejos , Ranitidina/farmacocinética
6.
Mult Scler Relat Disord ; 27: 397-399, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30508784

RESUMEN

BACKGROUND: Ocrelizumab is a monoclonal antibody directed against CD20+ B cells that is approved for MS. The most common side effect is infusion-associated reactions (IARs). This study examines whether a modified premedication protocol reduces incidence of IARs and further examines predictors of IARs. METHODS: Patients took cetirizine 10 mg, ranitidine 75 mg, and increased hydration the night before the ocrelizumab infusion. This regimen was repeated the next day prior to arrival. Just prior to the infusion, patients were pretreated with IV diphenhydramine 50 mg, IV methylprednisolone 125 mg, and oral acetaminophen 650 mg. Rates of IARs with this modified protocol were compared to patients who had received only pretreatment medications. RESULTS: 207 patients received ocrelizumab. With the modified premedication protocol, we found significant decreased odds of IARs (OR 0.40, p = 0.024, 95% CI (0.18, 0.88). Among the baseline characteristics, there was a significant reduction of IARs with increasing age (OR 0.94, p = 0.001) and male sex (OR 0.34, p = 0.034). Body mass index (BMI) increased the odds of IARs (OR 1.07, p = 0.029). Race and smoking status did not affect IARs. CONCLUSION: The modified premedication protocol described herein significantly decreases rates of IARs by 60% and suggests that the additional premedication regimen is beneficial. Age and male sex are protective for IARs while BMI is a risk factor for IARs.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/efectos adversos , Esclerosis Múltiple/tratamiento farmacológico , Premedicación , Acetaminofén/administración & dosificación , Administración Intravenosa , Adulto , Factores de Edad , Antiinflamatorios/administración & dosificación , Índice de Masa Corporal , Cetirizina/administración & dosificación , Difenhidramina/administración & dosificación , Femenino , Humanos , Masculino , Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Ranitidina/administración & dosificación , Factores Sexuales , Resultado del Tratamiento , Adulto Joven
7.
J Comp Eff Res ; 7(5): 493-501, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29775083

RESUMEN

AIM: Adequacy of enteral nutrition (EN) alone as stress ulcer prophylaxis (SUP) is controversial. The aim of this study was to compare efficacy of EN alone and ranitidine plus EN as SUP. METHOD: Critically ill adults with indications to receive SUP were randomized to ranitidine 50 mg IV every 8 h plus EN (SUP) or EN alone (non-SUP) group for 7 days. Besides, endoscopy was performed at the time of recruitment and on day 7. RESULTS: During the study period, only one patient in each group of SUP and non-SUP experienced gastrointestinal bleeding. At the time of recruitment, gastric erosion and erythema were the most endoscopic findings in the SUP and non-SUP groups. These findings did not significantly change at the end of the study (p = 0.21). CONCLUSION: EN was at least effective as ranitidine plus EN as SUP.


Asunto(s)
Enfermedad Crítica , Nutrición Enteral/métodos , Úlcera Péptica/prevención & control , Ranitidina/administración & dosificación , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Endoscopía Gastrointestinal , Femenino , Mucosa Gástrica/patología , Hemorragia Gastrointestinal/etiología , Humanos , Masculino , Persona de Mediana Edad , Úlcera Péptica/complicaciones , Factores de Riesgo
8.
Br J Clin Pharmacol ; 84(7): 1611-1616, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29667234

RESUMEN

The anaphylactoid reaction described follows cessation of ranitidine in a 19-year-old female with the disease cluster: mast cell activation syndrome, hypermobile Ehlers-Danlos syndrome and postural tachycardia syndrome. Anaphylaxis can give wide-ranging symptoms from rhinorrhoea and urticaria to tachycardia and system-wide, life-threatening, anaphylactic shock. Individuals with a disorder of mast cell activation can experience many such symptoms. H2 receptor antagonists, such as ranitidine, are commonly prescribed in this population. A mechanism for the reaction is proposed in the context of ranitidine, as an inverse agonist, causing upregulation of H2 histamine receptors and raised histamine levels due to enzyme induction. This effect, following extended and/or high antihistamine dosing, may have implications for other individuals with a disorder of mast cell activation, such as mastocytosis or mast cell activation syndrome. There are potential policy and patient guidance implications for primary and secondary care with respect to cessation of H2 antagonists.


Asunto(s)
Anafilaxia/inmunología , Histamina/sangre , Receptores Histamínicos H2/metabolismo , Privación de Tratamiento , Adulto , Anafilaxia/sangre , Anafilaxia/diagnóstico , Anafilaxia/tratamiento farmacológico , Clorfeniramina/uso terapéutico , Epinefrina/administración & dosificación , Femenino , Histamina/inmunología , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Antagonistas de los Receptores H2 de la Histamina/administración & dosificación , Humanos , Ranitidina/administración & dosificación , Receptores Histamínicos H2/inmunología , Resultado del Tratamiento , Regulación hacia Arriba , Adulto Joven
10.
Hematol Oncol ; 36(2): 399-406, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28983943

RESUMEN

The aim of this retrospective cohort study was to investigate the incidence of delayed methotrexate elimination in patients treated with high-dose methotrexate (≥1 g/m2 ) for haematological malignancy and to identify the impact of interacting drugs, especially proton-pump inhibitors (PPIs) and ranitidine. All patients treated with high-dose methotrexate over a 6 year period in the haematology department of the Lyon Sud University Hospital (Hospices Civils de Lyon, France) were included. Potential risk factors for delayed methotrexate elimination were tested in a generalized linear model by univariate analysis: patient age, gender, methotrexate dose, administration of PPI or ranitidine, and concomitant nephrotoxic drugs. A total of 412 cycles of methotrexate were administered to 179 patients. Proton-pump inhibitors were co-administered with methotrexate in 127 cycles and ranitidine in 192 cycles. Ninety-three cycles included no antacid drugs. A total of 918 plasma methotrexate assays were performed. Methotrexate concentrations were checked at 24 hours in 92% of cycles. Delayed methotrexate elimination was observed in 20.9% of cycles. A total of 63 cycles with delayed methotrexate elimination were only identified on plasma methotrexate measures at 72 hours: ie, plasma methotrexate was in the normal range at 24 and 48 hour post injection. Use of PPI/ranitidine or no antacid drugs did not increase risk of delayed elimination, with respectively delayed methotrexate elimination in 20.5%, 21.9%, and 19.4% of cycles (P = .89). Impaired baseline creatinine clearance showed significant association in univariate analysis. Fifteen patients showed grade 1 acute kidney injury, 1 grade 2, 2 grade 3, and none grade 4. For half of these cases, delayed methotrexate elimination was observed and the 2 grade 3 events appeared in patients treated with PPIs. This retrospective study suggests that there is no association between concomitant use of proton-pump inhibitors (pantoprazole and esomeprazole) or ranitidine and delayed methotrexate elimination.


Asunto(s)
Metotrexato/farmacocinética , Inhibidores de la Bomba de Protones/farmacología , Ranitidina/farmacología , Adulto , Anciano , Antiulcerosos/administración & dosificación , Antiulcerosos/farmacología , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Interacciones Farmacológicas , Femenino , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/metabolismo , Humanos , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Inhibidores de la Bomba de Protones/administración & dosificación , Ranitidina/administración & dosificación , Estudios Retrospectivos , Factores de Tiempo
11.
BMJ Support Palliat Care ; 7(3): 255-257, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28159802

RESUMEN

Delayed gastric emptying in the presence or absence of mechanical bowel obstruction can cause distressing symptoms in palliative care patients. We present two patients, both with vomiting due to delayed gastric emptying and gastric outlet obstruction secondary to pancreatic cancer, treated with subcutaneous ranitidine resulting in a symptomatic response. We hypothesise that ranitidine is a useful adjunct to standard treatment with prokinetic agents or octreotide in such patients and potentially those with proximal mechanical bowel obstruction from other malignancies with associated delayed gastric emptying.


Asunto(s)
Fármacos Gastrointestinales/uso terapéutico , Gastroparesia/diagnóstico , Octreótido/uso terapéutico , Ranitidina/uso terapéutico , Adenocarcinoma/secundario , Anciano , Femenino , Fármacos Gastrointestinales/administración & dosificación , Gastroparesia/tratamiento farmacológico , Gastroparesia/etiología , Humanos , Inyecciones Subcutáneas , Neoplasias Pulmonares/secundario , Octreótido/administración & dosificación , Cuidados Paliativos , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/patología , Ranitidina/administración & dosificación
12.
Mediators Inflamm ; 2016: 1903849, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27057092

RESUMEN

Anthraquinone compounds are one of the abundant polyphenols found in fruits, vegetables, and herbs. However, the in vivo anti-inflammatory activity and molecular mechanisms of anthraquinones have not been fully elucidated. We investigated the activity of anthraquinones using acute inflammatory and nociceptive experimental conditions. Anthraquinone-2-carboxylic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA), one of the major anthraquinones identified from Brazilian taheebo, ameliorated various inflammatory and algesic symptoms in EtOH/HCl- and acetylsalicylic acid- (ASA-) induced gastritis, arachidonic acid-induced edema, and acetic acid-induced abdominal writhing without displaying toxic profiles in body and organ weight, gastric irritation, or serum parameters. In addition, AQCA suppressed the expression of inflammatory genes such as cyclooxygenase- (COX-) 2 in stomach tissues and lipopolysaccharide- (LPS-) treated RAW264.7 cells. According to reporter gene assay and immunoblotting analyses, AQCA inhibited activation of the nuclear factor- (NF-) κB and activator protein- (AP-) 1 pathways by suppression of upstream signaling involving interleukin-1 receptor-associated kinase 4 (IRAK1), p38, Src, and spleen tyrosine kinase (Syk). Our data strongly suggest that anthraquinones such as AQCA act as potent anti-inflammatory and antinociceptive components in vivo, thus contributing to the immune regulatory role of fruits and herbs.


Asunto(s)
Analgésicos/uso terapéutico , Antraquinonas/uso terapéutico , Antiinflamatorios/uso terapéutico , Ácido Acético/farmacología , Analgésicos/administración & dosificación , Animales , Antraquinonas/administración & dosificación , Antiinflamatorios/administración & dosificación , Ácido Araquidónico/farmacología , Ciclooxigenasa 2/metabolismo , Edema/inducido químicamente , Edema/tratamiento farmacológico , Lipopolisacáridos/farmacología , Masculino , Ratones , Ratones Endogámicos ICR , FN-kappa B/metabolismo , Extractos Vegetales/química , Células RAW 264.7 , Ranitidina/administración & dosificación , Ranitidina/uso terapéutico , Transducción de Señal/efectos de los fármacos
13.
Carcinogenesis ; 37(6): 625-634, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26992900

RESUMEN

The H2-receptor antagonist, ranitidine, is among the most widely used pharmaceuticals to treat gastroesophageal reflux disease and peptic ulcers. While previous studies have demonstrated that amines can form N-nitrosamines when exposed to nitrite at stomach-relevant pH, N-nitrosamine formation from ranitidine, an amine-based pharmaceutical, has not been demonstrated under these conditions. In this work, we confirmed the production of N-nitrosodimethylamine (NDMA), a potent carcinogen, by nitrosation of ranitidine under stomach-relevant pH conditions in vitro We also evaluated the urinary NDMA excretion attributable to ingestion of clinically used ranitidine doses. Urine samples collected from five female and five male, healthy adult volunteers over 24-h periods before and after consumption of 150mg ranitidine were analyzed for residual ranitidine, ranitidine metabolites, NDMA, total N-nitrosamines and dimethylamine. Following ranitidine intake, the urinary NDMA excreted over 24h increased 400-folds from 110 to 47 600ng, while total N-nitrosamines increased 5-folds. NDMA excretion rates after ranitidine intake equaled or exceeded those observed previously in patients with schistosomiasis, a disease wherein N-nitrosamines are implicated as the etiological agents for bladder cancer. Due to metabolism within the body, urinary NDMA measurements represent a lower-bound estimate of systemic NDMA exposure. Our results suggest a need to evaluate the risks attributable to NDMA associated with chronic consumption of ranitidine, and to identify alternative treatments that minimize exposure to N-nitrosamines.


Asunto(s)
Dimetilnitrosamina/orina , Ranitidina/administración & dosificación , Ranitidina/farmacocinética , Administración Oral , Adulto , Carcinógenos/farmacocinética , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Nitrosaminas/farmacocinética , Nitrosaminas/orina , Adulto Joven
14.
Chem Pharm Bull (Tokyo) ; 64(1): 42-51, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26726743

RESUMEN

Carbopol (CP) is a biocompatible bioadhesive polymer used as a matrix for gastroretentive (GR) tablets, however, its rapid hydration shortens its bioadhesion and floating when incorporated in effervescent formulae. The interpolymer complexation of CP with polyvinylpyrrolidone (PVP) significantly reduced the excessive hydration of CP, prolonging floating and maintaining the mucoadhesiveness. In early attempts, a lengthy process was followed to prepare such an interpolymer complex. In this study, an in situ interpolymer complexation between CP and two grades of PVP (K25 and K90) in 0.1 N HCl was investigated and characterized by Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Hence, directly compressed GR tablets of different combinations of PVP and CP with sodium bicarbonate (SB) as an effervescent agent were examined for prolonged gastroretention and sustained release of ranitidine hydrochloride (RHCl) as a model drug. Tablets were evaluated for in vitro buoyancy, bioadhesiveness, swelling, and drug release in 0.1 N HCl. All GR tablets containing PVP-CP combinations achieved more prolonged floating (>24 h) than CP tablets (5.2 h). Their bioadhesiveness, swelling, and drug release were dependent on the PVP molecular weight and its ratio to CP. Drug release profiles of all formulae followed non-Fickian diffusion. Formula containing the PVP K90-CP combination at a respective ratio of 1 : 3 (P90C13) was a promising system, exhibiting good floating and bioadhesive properties as well as sustained drug release. Abdominal X-ray imaging of P90C13 formula, loaded with barium sulfate, in six healthy volunteers showed a mean gastric retention period of 6.8±0.3 h.


Asunto(s)
Resinas Acrílicas/química , Antiulcerosos/administración & dosificación , Antiulcerosos/farmacocinética , Povidona/química , Ranitidina/administración & dosificación , Ranitidina/farmacocinética , Resinas Acrílicas/administración & dosificación , Resinas Acrílicas/farmacocinética , Adulto , Antiulcerosos/química , Liberación de Fármacos , Absorción Gastrointestinal , Voluntarios Sanos , Humanos , Cinética , Masculino , Povidona/administración & dosificación , Povidona/farmacocinética , Ranitidina/química , Bicarbonato de Sodio/administración & dosificación , Bicarbonato de Sodio/química , Bicarbonato de Sodio/farmacocinética , Comprimidos , Adulto Joven
16.
J Am Geriatr Soc ; 63(11): 2290-7, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26503124

RESUMEN

OBJECTIVES: To determine how many ambulatory older adults with chronic kidney disease receive medications that are contraindicated or dosed excessively given their level of renal function. DESIGN: Cross-sectional retrospective study. SETTING: U.S. Department of Veterans Affairs (VA) clinics. PARTICIPANTS: Individuals aged 65 and older with a creatinine clearance (CrCl) of 15 to 49 mL/min (N = 83,850; mean age 80; 96% male). MEASUREMENTS: Forty medications that require dose adjustment or are contraindicated in people with impaired renal function were examined. Medication use and CrCl (calculated using the Cockroft-Gault equation) were assessed using VA pharmacy, laboratory, and other data sources as of October 2007. RESULTS: Thirteen percent of older veterans with a CrCl of 30 to 49 mL/min and 32% of those with a CrCl of 15 to 29 mL/min received one or more drugs that were contraindicated or prescribed at an excessive dose given the individual's level of renal function. The strongest risk factor for renally inappropriate prescribing was number of medications used; the risk of receiving renally inappropriate medications was 5.5 times as high (95% confidence interval = 5.1-5.9) in older adults taking 10 or more medications as in those taking one to three medications. Ranitidine, allopurinol, and metformin together accounted for 76% of renally misprescribed medications in individuals with a CrCl of 30 to 49 mL/min. Glyburide, ranitidine, gemfibrozil, carvedilol, and allopurinol accounted for 47% of renally misprescribed drugs for individuals with a CrCl of 15 to 29 mL/min. CONCLUSION: Inappropriate prescribing of renally cleared medications is common in ambulatory older veterans, with only a few medications accounting for most of these prescribing problems.


Asunto(s)
Prescripción Inadecuada/estadística & datos numéricos , Insuficiencia Renal Crónica/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Alopurinol/administración & dosificación , Aminohidrolasas , Peso Corporal , Comorbilidad , Estudios Transversales , Femenino , Humanos , Masculino , Metformina/administración & dosificación , Ranitidina/administración & dosificación , Estudios Retrospectivos , Estados Unidos , Veteranos
17.
J Clin Anesth ; 27(5): 396-400, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25935831

RESUMEN

INTRODUCTION: The anesthetic management of patients with morbid obesity is challenging. There is no consensus on the routine use of aspiration prophylaxis in morbidly obese patients undergoing elective surgery. AIM: The aim of this study is to assess the risk of pulmonary aspiration and effect of premedication with ranitidine and metoclopramide on gastric pH and volume in morbidly obese and lean patients. METHODS: Gastric volume and pH were measured in 3 groups of 20 patients each: group I (lean, no aspiration prophylaxis), group II (morbidly obese, no aspiration prophylaxis), and group III (morbidly obese; tablet ranitidine, 150 mg; and tablet metoclopramide, 10 mg administered the night before and 2 hours before surgery). Patients with critical gastric volume >25 mL and critical pH <2.5 (Roberts and Shirley criteria) were considered to be at risk for pulmonary aspiration. RESULTS: The percentage of patients with gastric volume >25 mL and pH <2.5 was 5%, 30%, and 0% in groups I, II, and III, respectively. Statistically significant difference existed between groups I and II (P = .04) and groups II and III (P = .006). Premedicated morbidly obese and lean patients were comparable (P = .46). CONCLUSION: Morbidly obese patients undergoing elective surgery are at a higher risk for regurgitation and pulmonary aspiration when compared with lean patients. Preoperative aspiration prophylaxis decreases gastric volume and increases gastric pH and thus should be routinely prescribed.


Asunto(s)
Metoclopramida/administración & dosificación , Obesidad Mórbida/complicaciones , Neumonía por Aspiración/prevención & control , Ranitidina/administración & dosificación , Adulto , Antieméticos/administración & dosificación , Procedimientos Quirúrgicos Electivos/métodos , Femenino , Mucosa Gástrica/metabolismo , Antagonistas de los Receptores H2 de la Histamina/administración & dosificación , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Delgadez
18.
Pesqui. vet. bras ; 34(supl.1): 17-22, dez. 2014. tab, graf
Artículo en Inglés | LILACS, VETINDEX | ID: lil-778352

RESUMEN

Brazilian sheep production has intensified, predisposing sheep to an increased incidence of digestive disorders, such as abomasal ulcers. Ranitidine is used to prevent and treat this disease; however, there is little information on the parenteral use of this drug in adult ruminants. Few data exist on the concomitant metabolic changes and the behavior of the digestive system associated with its use. For this study, five healthy male sheep with ruminal and abomasal cannulas were used. A 5x5 Latin square experiment with a 2x2+1 factorial arrangement of the treatments was performed. Sheep treated with drug doses of 1 or 2mg/kg ranitidine administered intravenously every 8 or 12 hours were compared with the control group, was treated intravenously with 1 mL of physiological solution per 25 kg every 12 hours. Higher total protein concentrations, hemoglobin levels, as well as increased aspartate aminotransferase activity and increased abomasal pH for up to 150 min following drug administration were observed in all animals that received the drug, regardless of dose and frequency. The animals treated every 12 hours showed a decrease in leukocyte number compared with the control group and with the animals treated every 8 hours. Increased serum creatinine concentrations were observed in the animals treated every 8 hours. Treatments of 1mg/kg every 8 hours and 2mg/kg every 12 hours increased the red blood cell count and decreased the serum pepsinogen. All protocols studied were safe for healthy sheep, but 1mg/kg ranitidine every 8 hours and 2mg/kg ranitidine every 12 hours were the most effective protocols for gastric protection.(AU)


A ovinocultura brasileira tem se intensificado, o que predispõe os animais à maior incidência de transtornos digestivos, como a úlcera de abomaso. A ranitidina é utilizada na prevenção e tratamento desta afecção, no entanto há pouca informação sobre a indicação parenteral deste fármaco para ruminantes adultos. São escassas as informações a respeito das alterações metabólicas e do comportamento do sistema digestório associados ao seu uso. Para este estudo foram utilizados cinco ovinos, machos, hígidos, providos de cânula ruminal e abomasal. O delineamento foi Quadrado Latino 5x5 com arranjo fatorial de tratamentos 2x2+1. Os ovinos tratados com as doses de 1 e 2mg/kg de ranitidina administrada por via intravenosa a cada 8 ou 12 horas foram comparados aos animais do grupo controle, tratados por via intravenosa com 1mL de solução fisiológica por 25 kg a cada 12 horas. Maiores concentrações de proteína total e hemoglobina, maiores atividades de AST e aumento do pH abomasal por até 150 minutos foram observados em todos os animais que receberam o fármaco, independentemente de dose e frequência. Os animais tratados a cada 12 horas mostraram diminuição do número de leucócitos comparados aos animais tratados a cada 8 horas e aos animais do grupo controle. Observou-se aumento das concentrações de creatinina nos animais tratados a cada 8 horas. Os tratamentos 1mg/kg a cada 8 horas e 2mg/kg a cada 12 horas aumentaram o número de hemácias e diminuíram as concentrações séricas de pepsinogênio. Todos os protocolos estudados foram seguros para ovinos sadios, porém 1mg/kg de ranitidina a cada 8 horas e 2mg/kg a cada 12 horas mostraram-se mais eficientes quanto à proteção gástrica.


Asunto(s)
Animales , Ranitidina/administración & dosificación , Rumen/química , Abomaso/química , Ovinos/metabolismo , Inyecciones Intravenosas/veterinaria
19.
Rev Esp Anestesiol Reanim ; 61(7): 375-81, 2014.
Artículo en Español | MEDLINE | ID: mdl-24931134

RESUMEN

Type III hereditary angioedema is a rare familial disorder that has recently been described as a separate condition. Triggers for episodes of angioedema include surgery, dental procedures, and tracheal intubation maneuvers. Since episodes affecting the upper airway are potentially life-threatening, prophylactic treatment is recommended in these situations. The use of icatibant (Firazyr(®)), for prevention of angioedema prior to tracheal intubation, is reported in a patient with type iii hereditary angioedema. A literature review on the anesthetic management of this condition was conducted.


Asunto(s)
Antagonistas del Receptor de Bradiquinina B2/uso terapéutico , Bradiquinina/análogos & derivados , Angioedema Hereditario Tipo III/complicaciones , Intubación Intratraqueal , Edema Laríngeo/prevención & control , Atención Perioperativa/métodos , Medicación Preanestésica , Adulto , Obstrucción de las Vías Aéreas/tratamiento farmacológico , Obstrucción de las Vías Aéreas/etiología , Bradiquinina/administración & dosificación , Bradiquinina/uso terapéutico , Antagonistas del Receptor de Bradiquinina B2/administración & dosificación , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/secundario , Carcinoma Ductal de Mama/cirugía , Neoplasias Cerebelosas/secundario , Neoplasias Cerebelosas/cirugía , Clorfeniramina/administración & dosificación , Clorfeniramina/uso terapéutico , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Femenino , Humanos , Edema Laríngeo/tratamiento farmacológico , Edema Laríngeo/etiología , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/etiología , Hemorragia Posoperatoria/etiología , Ranitidina/administración & dosificación , Ranitidina/uso terapéutico , Respiración Artificial , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/terapia , Traqueostomía
20.
Pediatrics ; 133(6): E1518-24, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24864182

RESUMEN

OBJECTIVE: Caustic substance ingestion in childhood is a public health issue in developing countries, and several management protocols have been proposed to prevent the resulting esophageal strictures. The role of corticosteroids in preventing corrosive-induced strictures is controversial. Our aim was to study the influence of high doses of corticosteroids in preventing esophageal strictures. METHODS: Eighty-three children with a mean age of 4.10 6 2.63 years and with grade IIb esophageal burns (an esophagogastroscopy was performed within 24­48 hours of injury) due to corrosive substance ingestion were enrolled in our study between 2005 and 2008. Forty-two children (study group) received methylprednisolone (1 g/1.73 m2 per day for 3 days), ranitidine, ceftriaxone, and total parenteral nutrition. Forty-one children (control group) were administered the same regimen excluding methylprednisolone. Stricture development was compared between groups based on endoscopic and radiologic findings. RESULTS: During the endoscopic examination, stricture development was observed in 4 patients (10.8%) in the study group and in 12 patients (30%) in the control group. The difference was statistically significant (P = .038). The stricture development rate in the upper gastrointestinal system with barium meal was 14.3% and 45.0% in the study and control groups, respectively. The difference was statistically significant (P = .004). The duration of total parenteral nutrition was shorter in the study group compared with the control group (P = .001). High doses of methylprednisolone were well tolerated in the study group without any side effects. CONCLUSIONS: High doses of methylprednisolone used for the management of grade IIb esophageal burns may reduce stricture development.


Asunto(s)
Quemaduras Químicas/tratamiento farmacológico , Cáusticos/toxicidad , Estenosis Esofágica/inducido químicamente , Estenosis Esofágica/prevención & control , Esófago/efectos de los fármacos , Esófago/lesiones , Metilprednisolona/administración & dosificación , Quemaduras Químicas/clasificación , Quemaduras Químicas/complicaciones , Ceftriaxona/administración & dosificación , Niño , Preescolar , Terapia Combinada , Relación Dosis-Respuesta a Droga , Esofagoscopía , Femenino , Humanos , Infusiones Intravenosas , Masculino , Nutrición Parenteral Total , Pronóstico , Ranitidina/administración & dosificación , Turquía
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