RESUMEN
BACKGROUND: Although multiple linear regression-based limited sampling strategies (LSSs) have been published for enteric-coated mycophenolate sodium, none have been evaluated for the prediction of subsequent mycophenolic acid (MPA) exposure. This study aimed to examine the predictive performance of the published LSS for the estimation of future MPA area under the concentration-time curve from 0 to 12 hours (AUC0-12) in renal transplant recipients. METHODS: Total MPA plasma concentrations were measured in 20 adult renal transplant patients on 2 occasions a week apart. All subjects received concomitant tacrolimus and were approximately 1 month after transplant. Samples were taken at 0, 0.33, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours and 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 9, and 12 hours after dose on the first and second sampling occasion, respectively. Predicted MPA AUC0-12 was calculated using 19 published LSSs and data from the first or second sampling occasion for each patient and compared with the second occasion full MPA AUC0-12 calculated using the linear trapezoidal rule. Bias (median percentage prediction error) and imprecision (median absolute prediction error) were determined. RESULTS: Median percentage prediction error and median absolute prediction error for the prediction of full MPA AUC0-12 were <15% for 4 LSSs, using the data from the same (second) occasion. One equation (1.583C1 + 0.765C2 + 0.369C2.5 + 0.748C3 + 1.518C4 + 2.158C6 + 3.292C8 + 3.6690) showed bias and imprecision <15% for the prediction of future MPA AUC0-12, where the predicted AUC0-12 from the first occasion was compared with the full AUC0-12 from the second. All LSSs with an acceptable predictive performance included concentrations taken at least 6 hours after the dose. CONCLUSIONS: Only one LSS had an acceptable bias and precision for future estimation. Accurate dosage prediction using a multiple linear regression-based LSS was not possible without concentrations up to at least 8 hours after the dose.
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Trasplante de Riñón/estadística & datos numéricos , Ácido Micofenólico/farmacocinética , Comprimidos Recubiertos/farmacocinética , Comprimidos Recubiertos/uso terapéutico , Receptores de Trasplantes/estadística & datos numéricos , Australia , Femenino , Humanos , Inmunosupresores/administración & dosificación , Modelos Lineales , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/sangre , Tamaño de la Muestra , Tacrolimus/administración & dosificaciónRESUMEN
AIMS/HYPOTHESES: Glucagon-like peptide-1 (GLP-1), an important mediator of postprandial glycaemia, could potentially be stimulated by delivering small quantities of nutrient to a long length of distal gut. We aimed to determine whether enteric-coated pellets, releasing small amounts of lauric acid throughout the ileum and colon, could reduce glycaemic responses to meals in type 2 diabetes, associated with stimulation of GLP-1. METHODS: Eligible patients, who had type 2 diabetes controlled by diet or metformin, were each studied on two occasions in a hospital setting. After an overnight fast, patients consumed 5 g active pellets (47% lauric acid by weight) or placebo with breakfast (T = 0 min) and lunch (T = 240 min), in a crossover design with order randomised by the hospital pharmacy and allocation concealed by numbered containers. Patients and investigators making measurements were blinded to the intervention. Blood was sampled frequently for blood glucose (the primary outcome) and hormone assays. RESULTS: Eight patients were randomised (four to receive either intervention first), and all completed the study without adverse effects. Blood glucose was lower after breakfast (T = 0-240 min, area under the curve (AUC) 2,075 ± 368 vs 2,216 ± 163 mmol/l × min) and lunch (T = 240-480 min, AUC 1,916 ± 115 vs 2,088 ± 151 mmol/l × min) (p = 0.02 for each) after active pellets than after placebo. Plasma GLP-1 concentrations were higher after breakfast (p = 0.08) and lunch (p = 0.04) for active pellets. While there were no differences in insulin or glucose-dependent insulinotropic polypeptide concentrations, glucagon concentrations were higher after breakfast and lunch (p = 0.002 for each) for active pellets. CONCLUSIONS/INTERPRETATION: Delivering small amounts of nutrient to the ileum and colon can stimulate substantial endogenous GLP-1 release and attenuate postprandial glycaemia. This novel approach has therapeutic potential in type 2 diabetes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000600842. FUNDING: The study was funded by Meyer Nutriceuticals.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/metabolismo , Hiperglucemia/complicaciones , Comprimidos Recubiertos/uso terapéutico , Área Bajo la Curva , Glucemia/metabolismo , Colon/metabolismo , Estudios Cruzados , Femenino , Glucagón/metabolismo , Humanos , Íleon/metabolismo , Insulina/metabolismo , Ácidos Láuricos/uso terapéutico , Masculino , Metformina/uso terapéutico , Persona de Mediana Edad , Factores de TiempoRESUMEN
BACKGROUND: Short-term intensified dosing using enteric-coated mycophenolate sodium (EC-MPS) reduces rejection after kidney transplantation without compromising safety and may facilitate steroid avoidance. METHODS: In a 6-month, multicentre open-label trial, 222 de novo kidney transplant recipients at low-immunological risk were randomized to steroid avoidance or maintenance steroids with interleukin (IL)-2 receptor antibody (IL-2RA) induction, EC-MPS (2160 mg/day to Week 6, 1440 mg/day thereafter) and cyclosporine. RESULTS: The primary end point; treatment failure at Month 6 [biopsy-proven acute rejection (BPAR), graft loss, death or loss to follow-up], occurred in 17.9% (20/112) of steroid-avoidance patients and 14.5% (16/110) of controls (difference 3.4%, 95% confidence interval -6.3 to 13.1, P = 0.47 for superiority testing). BPAR occurred in 11.6 and 7.3% of patients in the steroid-avoidance and control arms, respectively (P = 0.27). Creatinine clearance was similar at Month 6 (steroid-avoidance 56 ± 18 mL/min/1.73 m(2), controls 60 ± 22 mL/min/1.73 m(2), P = 0.34). Cytomegalovirus infection, as reported by investigators, occurred in 12.5% of steroid-avoidance patients and 22.7% of controls (P = 0.045). CONCLUSIONS: A regimen of early intensified EC-MPS dosing with calcineurin inhibitor and IL-2RA induction permits oral steroid avoidance in adult kidney transplant patients at low-immunological risk without compromising efficacy at 6 months' follow-up.
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Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Ácido Micofenólico/análogos & derivados , Insuficiencia Renal Crónica/terapia , Comprimidos Recubiertos/uso terapéutico , Privación de Tratamiento , Adolescente , Corticoesteroides , Adulto , Anciano , Ciclosporina/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Pronóstico , Adulto JovenRESUMEN
The present study was designed to observe the effect of quadruple therapy combined with probiotics on Helicobacter pylori-related peptic ulcer. The patients in the control group (n = 90) were given regular quadruple therapy including proton pump inhibitor ilaprazole enteric-coated tablet + two antibiotics amoxicillin dispersible tablet and metronidazole tablet + colloidal bismuth pectin capsule for 2 weeks. Patients in the study group (n = 90) were given abovementioned quadruple therapy combined with probiotics live combined Bifidobacterium, Lactobacillus, and Enterococcus Capsules, oral for 2 weeks. Then Hp clearance rate, recurrence rate, levels of gastrointestinal hormone makers, and advance reactions between two groups were compared. At the 2nd week after the treatment, the Helicobacter pylori clearance rate in the study group (87.79%) was significantly higher than the control group (78.89%), and the total recurrence rate in the study group (6.67%) was significantly lower than the control group (13.33%) (P < 0.05). Serum gastrin and motilin expression were lower, and somatostatin expressions was significantly higher than those in the control group (P < 0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P > 0.05). In summary, quadruple therapy combined with probiotics in the treatment of Helicobacter pylori-related peptic ulcer can improve the Helicobacter pylori clearance rate, reduce the Helicobacter pylori recurrence rate, and is beneficial to improving the level of gastrointestinal hormones, with certain safety.
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Infecciones por Helicobacter , Helicobacter pylori , Úlcera Péptica , Probióticos , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Bismuto/farmacología , Bismuto/uso terapéutico , Metronidazol/farmacología , Metronidazol/uso terapéutico , Inhibidores de la Bomba de Protones/farmacología , Gastrinas/farmacología , Gastrinas/uso terapéutico , Motilina/farmacología , Motilina/uso terapéutico , Comprimidos Recubiertos/farmacología , Comprimidos Recubiertos/uso terapéutico , Quimioterapia Combinada , Úlcera Péptica/tratamiento farmacológico , Úlcera Péptica/microbiología , Amoxicilina/uso terapéutico , Amoxicilina/farmacología , Antibacterianos/uso terapéutico , Probióticos/uso terapéutico , Pectinas/farmacología , Pectinas/uso terapéutico , Somatostatina/farmacología , Somatostatina/uso terapéuticoRESUMEN
Conversion from MMF to EC-MPS may reduce GI complications and permit increased MPA dosing with a concomitant reduction in CNI dose. In a prospective trial, paediatric renal transplant patients with stable graft function were converted from MMF to EC-MPS and followed-up for 12 months. Data from 28 patients (mean age 13.9 +/- 3.1 yr) were available for analysis. Mean EC-MPS dose increased significantly from conversion to month 12 (668 +/- 81 mg/m(2)/day vs. 747 +/- 98 mg/m(2)/day, p < 0.001). CsA-ME dose (n = 23) decreased from 5.3 +/- 1.7 mg/kg/day at conversion to 4.6 +/- 1.4 mg/kg/day at month 12 (p = 0.010). cGFR increased from 69.5 +/- 23.3 mL/min/1.73 m(2) at the time of conversion to 80.7 +/- 30.7 mL/min/1.73 m(2) at month 12 (p = 0.007). The number of patients reporting at least one GI event during six months prior to conversion was 15/28 (53.6%), declining to 8/28 (28.6%) at month 6 post-conversion and 5/28 (17.8%) at month 12. This single-arm study suggests that conversion of paediatric renal transplant patients from MMF to EC-MPS does not compromise efficacy and leads to improved GI tolerability. MPA dose increased and CsA-ME dose decreased significantly, with an associated improvement in calculated GFR. A large-scale controlled trial is required to confirm these promising findings.
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Inmunosupresores/uso terapéutico , Trasplante de Riñón/métodos , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Comprimidos Recubiertos/uso terapéutico , Adolescente , Niño , Femenino , Tasa de Filtración Glomerular , Supervivencia de Injerto , Humanos , Masculino , Ácido Micofenólico/metabolismo , Estudios Prospectivos , Resultado del TratamientoRESUMEN
EC-MPS was designed to improve MPA-related GII because of MMF, by delaying the release of MPA until reaching the small intestine. At present, its immunosuppressive activity in pediatric renal transplant recipients with GII has not been clarified. We studied eight renal transplant recipients before and after three months of the conversion from MMF to equimolar doses of EC-MPS. After three months of treatment with EC-MPA, GII decreased between 100% and 12.5%. The predose levels of MPA were about 60% higher on EC-MPS (6.9 +/- 1.1 microg/mL) compared with MMF administration (4.2 +/- 0.9 microg/mL). Hemoglobin decreased significantly post-conversion (12.0 +/- 0.4 to 11.0 +/- 0.5 g/dL). Serum creatinine, creatinine clearance, and urinary protein excretion did not change. Also, proliferative response and cytotoxic antibodies showed no significant change. The release of interleukin-10 was strikingly augmented with MMF or EC-MPS therapy; meanwhile, gamma-interferon and TNF were low under both treatments. Our data indicate that conversion from MMF to EC-MPS leads to an improvement in GII without altering key elements of immunosuppression.
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Biomarcadores/metabolismo , Trasplante de Riñón/métodos , Ácido Micofenólico/análogos & derivados , Adolescente , Niño , Preescolar , Creatinina/sangre , Citocinas/metabolismo , Preparaciones de Acción Retardada/uso terapéutico , Femenino , Hemoglobinas/metabolismo , Humanos , Sistema Inmunológico , Interferón gamma/metabolismo , Masculino , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/uso terapéutico , Comprimidos Recubiertos/uso terapéutico , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/metabolismoAsunto(s)
Aspirina/administración & dosificación , Aspirina/efectos adversos , Hemorragia Gastrointestinal/inducido químicamente , Inhibidores de Agregación Plaquetaria/administración & dosificación , Accidente Cerebrovascular/prevención & control , Comprimidos Recubiertos/uso terapéutico , Administración Oral , Antiinflamatorios no Esteroideos/administración & dosificación , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/prevención & control , Comprimidos Recubiertos/efectos adversosRESUMEN
The introduction of mycophenolate as an adjuvant in immunosuppressive regimes has improved clinical outcomes of transplant patients due to a reduced incidence of acute rejection episodes. Nevertheless, the need for dose adjustments or therapy discontinuations (up to 45% in some series), have downgraded the efficacy of mycophenolate mofetil (MMF). From October 2003 to April 2005, 36 kidney transplantations were performed at our site. The immunosuppressive protocol included induction with basiliximab, administered on days 0 and 4 posttransplantation, cyclosporine microemulsion (CsA-ME) monitored by concentrations at 2 hours (C2), enteric-coated sodium mycophenolate (EC-MPS; 720 +/- 180 mg bid), and steroids. Mean follow-up time was 7.3 +/- 4.4 months. Fourteen patients (38.9%) experienced delayed graft function (DGF). Seven (19%) episodes of acute rejection included 5 graded as I-A, 1 as grade I-B, and 1 as grade II-A. There were discontinuations of EC-MPS. Regarding gastrointestinal (GI) adverse events, there were 2 episodes of noninfectious diarrhea, 1 gastritis, and 1 upper GI hemorrhage. There were 11 infections: 4 in the urinary tract; 3 in the lung; 3 in the GI tract; and 1 CMV infection. There were no discontinuations of EC-MPS reported [corrected] Two (6%) graft losses were reported to be due to sepsis. In this group of patients who experienced a high incidence of DGF, the combination of basiliximab, CsA-ME (monitored by C2), and EC-MPS resulted in low Banff grade acute rejection episodes which were all responsive to steroids. The incidence of GI adverse events was only 11%.
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Trasplante de Riñón/fisiología , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/uso terapéutico , Comprimidos Recubiertos/uso terapéutico , Adulto , Anticuerpos Monoclonales/uso terapéutico , Basiliximab , Creatinina/sangre , Ciclosporina/uso terapéutico , Monitoreo de Drogas , Quimioterapia Combinada , Femenino , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Masculino , Persona de Mediana Edad , Ácido Micofenólico/efectos adversos , Proteínas Recombinantes de Fusión/uso terapéutico , Resultado del TratamientoRESUMEN
Preformulation is an important step in the rational formulation of an active pharmaceutical ingredient (API). Micromeritics properties: bulk density (BD) and tapped density (TD), compressibility index (Carr's index), Hauser's ratio (H), and sieve analysis were performed in order to determine the best excipients to be used in the formulation development of omeprazole magnesium enteric coated tablets. Results show that omeprazole magnesium has fair flow and compressibility properties (BD 0.4 g/mL, TD 0.485 g/mL, Carr's index 17.5%, Hauser's ratio 1.2, and sieve analysis time 5 minutes). There were no significant drug excipient interactions except change in colour in all three conditions in the mixture of omeprazole and aerosil 200. Moisture content loss on drying in all three conditions was not constant and the changes were attributed to surrounding environment during the test time. Changes in the absorption spectra were noted in the mixture of omeprazole and water aerosil only in the visible region of 350-2500 nm. Omeprazole magnesium alone and with all excipients showed no significant changes in omeprazole concentration for a 30-day period. Omeprazole magnesium formulation complies with USP standards with regards to the fineness, flowability, and compressibility of which other excipients can be used in the formulation.
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Disponibilidad Biológica , Química Farmacéutica , Omeprazol/uso terapéutico , Comprimidos Recubiertos/uso terapéutico , Humanos , Omeprazol/química , Omeprazol/farmacocinética , Dióxido de Silicio/química , Solubilidad , Comprimidos Recubiertos/química , Comprimidos Recubiertos/farmacocinética , Agua/químicaRESUMEN
BACKGROUND AND PURPOSE: Aspirin is used commonly to prevent ischemic strokes and other vascular events. Although aspirin is considered safe and effective, it has limited efficacy with a relative risk reduction of 20% to 25% for ischemic stroke. We sought to determine if aspirin as currently used is having its desired antiplatelet effects. METHODS: We ascertained patients with cerebrovascular disease who were taking only aspirin as an antiplatelet agent. Platelet function was evaluated using a platelet function analyzer (PFA-100). PFA test results were correlated with aspirin dose, formulation, and basic demographic factors. RESULTS: We ascertained 129 patients, of whom 32% were taking an enteric-coated aspirin preparation and 32% were taking low-dose (< or =162 mg/d) aspirin. For the entire cohort, 37% of patients had normal PFA-100 results, indicating normal platelet function. For the patients taking low-dose aspirin, 56% had normal PFAs compared with 28% of those taking > or =325 mg/d of aspirin, while 65% of patients taking enteric-coated aspirin had normal PFAs compared with 25% taking an uncoated preparation (P<0.01 for both comparisons). Similar results were obtained if PFA results were analyzed using mean closure times (low-dose aspirin, 183 sec; high-dose aspirin, 233 sec; enteric-coated, 173 sec; uncoated, 235 sec; P<0.01 for comparisons). Older patients and women were less likely to have a therapeutic response to aspirin, independent of aspirin dose or formulation. CONCLUSIONS: A significant proportion of patients taking low-dose aspirin or enteric-coated aspirin have normal platelet function as measured by the PFA-100 test. If these results correlate with clinical events, they have broad implications in determining how aspirin is used and monitored.
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Aspirina/farmacología , Plaquetas/efectos de los fármacos , Trastornos Cerebrovasculares/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/farmacología , Comprimidos Recubiertos/farmacología , Factores de Edad , Aspirina/uso terapéutico , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Resistencia a Medicamentos , Femenino , Humanos , Pacientes Internos , Ataque Isquémico Transitorio/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pacientes Ambulatorios , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pruebas de Función Plaquetaria , Estudios Prospectivos , Accidente Cerebrovascular/tratamiento farmacológico , Comprimidos Recubiertos/uso terapéuticoRESUMEN
Treatment of exocrine pancreatic insufficiency with the use of eight tablets of pancreatin with meals consisting of 25 g of fat per meal will generally abolish azotorrhea. Although steatorrhea is not totally corrected, satisfactory nutritional status and relative relief of symptoms are usually achieved. For the occasional patient who continues to lose weight or remains symptomatic even after reduction of dietary fat, the addition of cimetidine to the standard pancreatin treatment will usually provide relief from the steatorrhea and alleviate troublesome diarrhea. In certain circumstances in which gastric pH is more than 4 for 1 hour after a meal, altering the dosage schedule to two tablets hourly may be effective in alleviating the steatorrhea. Conversely, in patients whose upper gastrointestinal tract is acidic for long periods postprandially (gastric pH less than 5, duodenal pH less than 4), Pancrease, an enteric-coated preparation, may be effective. In difficult cases in which symptoms and steatorrhea continue, special intraluminal studies need to be performed to ensure that intraluminal conditions are, in fact, present for certain dosage schedules to be effective or that intraluminal conditions have been altered by adjunctive therapy.
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Enfermedades Pancreáticas/tratamiento farmacológico , Extractos Pancreáticos/uso terapéutico , Pancreatina/uso terapéutico , Enfermedad Celíaca/etiología , Duodeno/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Páncreas/enzimología , Enfermedades Pancreáticas/enzimología , Extractos Pancreáticos/administración & dosificación , Pancreatina/administración & dosificación , Comprimidos Recubiertos/uso terapéuticoRESUMEN
During an attack of ulcerative colitis the colonic pH of normally 6.4-7.0 drops to values of 2.3-4.7. The objective of this study was to investigate an acid-soluble polymer (Eudragit E) as coating material for multiple units (mini tablets) with regard to its ability to allow drug release only under the acidic conditions of the inflamed colon. Mini tablets (diameter 3 mm) containing 20% (w/w) of the model drug dexamethasone with or without the mucoadhesive swelling agent carbomer 934 (neutralized) were coated in a small coating pan with different amounts of an organic solution of Eudragit E leading to coating thicknesses of 150-400 microm. Drug release from the Eudragit E-coated cores at pH 2.0-5.0 starts after 10-50 min due to the rapid dissolution of the Eudragit E film. At pH 6.8 lag times of drug release depend on the composition of the cores and the thickness of the coating film: In the case of the carbomer-containing cores drug release is induced by disruption of the coating film due to swelling of the cores and lag times (up to 20 h) increase overproportionately with increasing coating thickness. With no swelling agent in the cores drug release at pH 6.8 is delayed due to the low erosion/dissolution rate of Eudragit E. Lag times of drug release (up to 33 h) increase in a linear manner with increasing coating thickness. Thus, Eudragit E, protected against dissolution in the stomach by an enteric coating, is a suitable coating polymer for drug release in acidic regions such as the inflamed colon.
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Química Farmacéutica/métodos , Preparaciones de Acción Retardada/química , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Polímeros/química , Comprimidos Recubiertos/uso terapéutico , Administración Tópica , Dexametasona/farmacocinética , Humanos , Concentración de Iones de Hidrógeno , SolubilidadAsunto(s)
Enfermedades de los Perros/tratamiento farmacológico , Insuficiencia Pancreática Exocrina/veterinaria , Extractos Pancreáticos/uso terapéutico , Animales , Perros , Método Doble Ciego , Insuficiencia Pancreática Exocrina/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Comprimidos Recubiertos/uso terapéuticoRESUMEN
BACKGROUND: GastroGard, an omeprazole powder paste formulation, is considered the standard treatment for gastric ulcers in horses and is highly effective. Gastrozol, an enteric-coated omeprazole formulation for horses, has recently become available, but efficacy data are controversial and sparse. OBJECTIVES: To investigate the efficacy of GastroGard and Gastrozol at labeled doses (4 and 1 mg of omeprazole per kg bwt, respectively, PO q24h) in healing of gastric ulcers. ANIMALS: 40 horses; 9.5 ± 4.6 years; 491 ± 135 kg. METHODS: Prospective, randomized, blinded study. Horses with an ulcer score ≥1 (Equine Gastric Ulcer Council) were randomly divided into 2 groups and treated for 2 weeks each with GastroGard followed by Gastrozol (A) or vice versa (B). After 2 and 4 weeks, scoring was repeated and compared with baseline. Plasma omeprazole concentrations were measured on the first day of treatment after administration of GastroGard (n = 5) or Gastrozol (n = 5). RESULTS: Compared with baseline (squamous score (A) 1.65 ± 0.11, (B) 1.98 ± 0.11), ulcer scores at 2 weeks ((A) 0.89 ± 0.11, (B) 1.01 ± 0.11) and 4 weeks ((A) 1.10 ± 0.12, (B) 0.80 ± 0.12) had significantly decreased in both groups (P < .001), independent of treatment (P = .7). Plasma omeprazole concentrations were significantly higher after GastroGard compared with Gastrozol administration (AUCGG = 2856 (1405-4576) ng/mL × h, AUCGZ = 604 (430-1609) ng/mL × h; P = .03). The bioavailability for Gastrozol was 1.26 (95% CI 0.56-2.81) times higher than for GastroGard. CONCLUSIONS AND CLINICAL IMPORTANCE: Both Gastrozol and GastroGard, combined with appropriate environmental changes, promote healing of gastric ulcers in horses. However, despite enteric coating of Gastrozol, plasma omeprazole concentrations after single labeled doses were significantly higher with GastroGard.
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Antiulcerosos/uso terapéutico , Enfermedades de los Caballos/tratamiento farmacológico , Omeprazol/uso terapéutico , Úlcera Gástrica/veterinaria , Animales , Antiulcerosos/administración & dosificación , Antiulcerosos/sangre , Antiulcerosos/farmacocinética , Femenino , Caballos , Masculino , Pomadas/uso terapéutico , Omeprazol/administración & dosificación , Omeprazol/sangre , Omeprazol/farmacocinética , Polvos/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Comprimidos Recubiertos/uso terapéuticoRESUMEN
This patent review focuses exclusively on the oral delivery of mesalamine (5-ASA) and excludes oral mesalamine pro-drug and rectal delivery formulations. The formulation strategies of marketed formulations (Apriso(®), Asacol(®), Lialda(®) and Pentasa(®)) and non-marketed formulations are reviewed and explained by decoding formulation specifics that enable the site specific delivery for the treatment of inflammatory bowel disease.
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Antiinflamatorios no Esteroideos/administración & dosificación , Química Farmacéutica/métodos , Sistemas de Liberación de Medicamentos/métodos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Mesalamina/administración & dosificación , Administración Oral , Antiinflamatorios no Esteroideos/uso terapéutico , Humanos , Mesalamina/uso terapéutico , Patentes como Asunto , Comprimidos Recubiertos/administración & dosificación , Comprimidos Recubiertos/uso terapéuticoRESUMEN
The purpose of this study was to assess the impact of enteric-coated mycophenolate sodium (EC-MPS) on skin and pulmonary manifestations of patients with progressive systemic sclerosis (Ssc). A prospective, open-label single-centre trial with EC-MPS 2 × 720 mg/day over 12 months and a long-term follow-up of 50 months were conducted. Modified Rodnan skin score (mRSS) was used to assess the skin and pulmonary function tests to assess the pulmonary involvement. In order to quantify the extent of alveolitis/fibrosis via densitometry, the high attenuation value, median lung density and percentiles of lung tissue densities were obtained by high-resolution computed tomography. Eleven patients were included. Three patients had to stop medication before month 6 (2× side effects, 1× progression). For the remaining eight patients, the median mRSS was non-significantly reduced from 13.5 at baseline to 11 at month 12. According to the CT histography, median lung density and high attenuation values remained stable. However, the course of percentiles -200 to -300 and particularly -300 to -400 Hounsfield units slightly increased in seven of eight patients after 12 months, suggesting worsening of pulmonary involvement. Accordingly, median diffusing capacity for carbon monoxide showed a tendency to decline (75.1 % vs. 70.2) while forced vital capacity non-significantly improved (78.0 vs. 85.5 %) during the study. Four patients are still on EC-MPS without clinical signs of progression after 50 months follow-up. EC-MPS showed non-significant improvement of the skin. Pulmonary fibrosis remained stable with only a slight tendency towards progression which might be ascribed to the medication as well as the natural course of the disease. CT histography appears to be a sensitive method for the detection of progression of pulmonary fibrosis and therefore should be considered for further studies in Ssc.
Asunto(s)
Ácido Micofenólico/análogos & derivados , Fibrosis Pulmonar/diagnóstico , Esclerodermia Difusa/tratamiento farmacológico , Comprimidos Recubiertos/uso terapéutico , Adulto , Anciano , Monóxido de Carbono/análisis , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/uso terapéutico , Estudios Prospectivos , Fibrosis Pulmonar/complicaciones , Fibrosis Pulmonar/tratamiento farmacológico , Pruebas de Función Respiratoria , Esclerodermia Difusa/complicaciones , Piel/patología , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Different oral formulations of 'mesalazine (mesalamine)' may have different efficacy in distal ulcerative colitis. AIM: To evaluate the efficacy of mesalazine granules (Salofalk granules) vs. mesalazine tablets (Salofalk tablets) as induction therapy in patients with distinct extensions of ulcerative colitis. METHODS: A pooled analysis of 705 patients from four prospective, randomised, double-blind phase III trials was performed. The efficacy of 8 weeks' induction with 3 g/day mesalazine granules [3 g once daily (o.d.) or 1 g three times daily (t.d.s)] vs. 3 g/day mesalazine tablets (1 g t.d.s.) was compared in terms of clinical remission (CR: CAI ≤ 4) and endoscopic remission (ER: EI ≤ 3) (both according to Rachmilewitz) in subgroups with pancolitis, left-sided colitis, or proctosigmoiditis. RESULTS: Mesalazine granules were equipotent to mesalazine tablets in pancolitis regarding CR (72% vs. 71%, P = 0.909) and ER (58% vs. 49%, P = 0.338). In left-sided colitis, both mesalazine formulations were equipotent regarding CR (66% vs. 67%; P = 0.843) but mesalazine granules were superior regarding ER (56% vs. 37%; P = 0.025). In proctosigmoiditis, mesalazine granules were significantly more effective than mesalazine tablets regarding CR (78% vs. 55% P < 0.001) and ER (67% vs. 43% P < 0.001). Furthermore, o.d. application of mesalazine granules was more effective than t.d.s. dosing in left-sided colitis (CR 73% vs. 62%, P = 0.181; ER 71% vs. 48% P = 0.005) and proctosigmoiditis (CR 86% vs. 73%, P = 0.020; ER 75% vs. 61%, P = 0.021), but not in pancolitis. CONCLUSION: This pooled analysis supports the hypothesis that mesalazine granules are superior to mesalazine tablets in induction of remission in distal colitis and should be taken once daily.