RESUMEN
OBJECTIVE: To determine whether prophylactic treatment with ursodeoxycholic acid can prevent gallstone formation in persons participating in a very-low-calorie weight reduction diet program. DESIGN: Multicenter, double-blind, placebo-controlled, multidose clinical trial. Patients were treated with placebo or with 300 mg/d, 600 mg/d, or 1200 mg/d of ursodeoxycholic acid. SETTING: 31 Health Management Resources weight management centers. PATIENTS: 1004 patients were initially enrolled in a 16-week, 520-kcal/d, Health Management Resources liquid protein diet program. All patients had a body mass index of 38 kg/m2 or more and a normal gallbladder ultrasonogram before study entry. Bile analysis was done in 32 patients. MEASUREMENTS: Body weight and body mass index were measured before the diet was started and at 2-week intervals for 16 weeks. Gallbladder ultrasonography was done before enrollment and after 8 and 16 weeks of dieting. Bile was obtained by endoscopy and analyzed for cholesterol crystals and lipid levels. RESULTS: Mean body weight for all patients at the start of dieting was 128.2 kg +/- 23.2 kg; mean initial body mass index was 44.2 kg/m2 +/- 6.0 kg/m2. Gallstones developed in 28% (95% CI, 22% to 35%) of patients receiving placebo, in 8% (CI, 5% to 13%) of patients treated with 300 mg/d of ursodeoxycholic acid, in 3% (CI, 1% to 7%) of patients treated with 600 mg/d of ursodeoxycholic acid, and in 2% (CI, 0.5% to 5%) of patients treated with 1200 mg/d of ursodeoxycholic acid. The differences between patients receiving placebo and patients receiving ursodeoxycholic acid were statistically significant. The percentage of ursodeoxycholic acid in bile increased stepwise with increasing doses of ursodeoxycholic acid. CONCLUSIONS: Ursodeoxycholic acid, 600 mg/d, is highly effective in preventing gallstone formation in patients having dietary-induced weight reduction.
Asunto(s)
Colelitiasis/prevención & control , Dieta Reductora , Ácido Ursodesoxicólico/uso terapéutico , Adolescente , Adulto , Anciano , Bilis/química , Índice de Masa Corporal , Colesterol/análisis , Cristalización , Método Doble Ciego , Ingestión de Energía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Ácido Ursodesoxicólico/efectos adversos , Pérdida de PesoRESUMEN
Ninety-two nonglaucomatous patients undergoing extracapsular cataract extraction with implantation of a posterior chamber intraocular lens by residents at a Veterans hospital were randomized in double-masked fashion to receive either a topical nonsteroidal antiinflammatory agent, diclofenac sodium 0.1%, or a placebo consisting of vehicle only. One drop of placebo or diclofenac sodium 0.1% was administered on an inpatient basis by trained staff every 6 hours for three doses, starting the afternoon prior to surgery. A further drop was given at 90, 60, 30, and 15 minutes before the operation. Starting 24 hours after surgery, all patients received diclofenac sodium 0.1%. All patients remained hospitalized for 72 hours postoperatively. Mean baseline intraocular pressure (IOP) was 14.0 and 14.1 mm Hg in the diclofenac and placebo groups, respectively. IOP rose 8.6 mm Hg in both groups at 6 hours after surgery. At 24 hours, the mean IOP elevation from baseline was 11.3 mm Hg in the diclofenac group and 9.6 mm Hg in the placebo group (P = .47). Within the first 24 hours, IOP spiked more than 10 mm Hg in 57% (26/46) of the diclofenac patients and in 54% (25/46) of the placebo patients. These results suggest that diclofenac sodium 0.1% drops affect neither the incidence nor the height of IOP elevation following cataract surgery.
Asunto(s)
Extracción de Catarata/efectos adversos , Diclofenaco/uso terapéutico , Presión Intraocular/efectos de los fármacos , Hipertensión Ocular/fisiopatología , Soluciones Oftálmicas/uso terapéutico , Anciano , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lentes Intraoculares , Masculino , Persona de Mediana Edad , Hipertensión Ocular/tratamiento farmacológico , Placebos , Resultado del TratamientoRESUMEN
This study compared the effects of diet and cimetidine on theophylline metabolism and examined interactions between these effects. Twelve men received a high-protein diet for 15 days and at another time a high-carbohydrate diet also for 15 days. Cimetidine, 800 mg daily at bedtime, was administered on days 10 through 15 of each dietary period. Theophylline metabolism was studied after the administration of a single intravenous 3 mg/kg dose on days 8 and 15 of each dietary period. Changing from a high-protein to a high-carbohydrate diet decreased theophylline clearance by about the same extent (30% +/- 10%) as treatment with cimetidine (37% +/- 5% during a high-protein diet and 30% +/- 5% during a high-carbohydrate diet). Cimetidine did not significantly influence the effects of diet on theophylline clearance. Conversely, dietary composition did not influence the degree of inhibition of theophylline metabolism induced by cimetidine. Depending on the direction of the change in protein/carbohydrate ratio, the effects of diet and cimetidine treatment were either additive (theophylline clearance was most prolonged during the high-carbohydrate regimen with concurrent cimetidine administration) or counteractive (increasing the dietary protein/carbohydrate ratio at least partially counteracted the inhibitory effect of cimetidine). In individual subjects, effects of cimetidine on theophylline metabolism were somewhat more consistent than diet-induced changes. The results are further evidence that diet and drugs can have similar effects on hepatic drug metabolism rates in humans. Variations in diet over time and individual differences in responses to diet may provide the potential for considerable instability of drug metabolism rates in free-living subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Cimetidina/farmacología , Carbohidratos de la Dieta/farmacología , Proteínas en la Dieta/farmacología , Hígado/metabolismo , Teofilina/farmacocinética , Adulto , Carbohidratos de la Dieta/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Semivida , Humanos , Hígado/efectos de los fármacos , MasculinoRESUMEN
The antipyrine (AP) test has been challenged in species other than humans on the grounds that, in some nonhuman species, particularly on induction, hepatic blood flow may become as prominent a factor in AP clearance as hepatic metabolism. Therefore, we investigated in dogs and monkeys the disposition of AP to determine how well AP serves as a model drug to indicate changes in rates of hepatic clearance. After administration of an oral solution of AP (5 mg/kg) to control dogs, the percentage of the dose absorbed was 98%, based on urinary and fecal excretion of AP and its metabolites. Despite complete AP absorption, absolute bioavailability of AP was 78 +/- 12% under basal conditions, suggesting that AP does undergo some degree of presystemic elimination, approximately 22%. After PB administration of 20 mg/kg/day for 9 days, po, AP bioavailability decreased to 60 +/- 14%. The systemic clearance of AP increased from 9.4 +/- 2.3 ml/min/kg under basal conditions to 27.5 +/- 4.6 ml/min/kg following PB. PB decreased mean plasma AP half-life from 71.5 min under basal conditions to 27.7 min, and mean hepatic blood flow increased from 0.49 liters/min to 0.63 liters/min. Induction doubled the hepatic extraction ratio for AP to 0.4 from 0.2 under basal conditions. In beagle dogs after PB pretreatment, 97% of the total systemic clearance of AP was estimated to be due to enhanced hepatic AP metabolism, only 3% to increased hepatic blood flow. Therefore, for dogs under both basal and induced conditions it is concluded that AP clearance reflects predominantly hepatic AP metabolism, being negligibly influenced by hepatic blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Antipirina , Perros/fisiología , Pruebas de Función Hepática , Macaca/fisiología , Administración Oral , Animales , Antipirina/farmacología , Disponibilidad Biológica , Cromatografía de Gases , Cromatografía Líquida de Alta Presión , Heces/análisis , Femenino , Infusiones Intravenosas , Factores de TiempoRESUMEN
The antiarrhythmic effect of timolol was investigated in 160 subjects with supraventricular arrhythmias. In our double-blind, randomized, parallel, multiclinic study, subjects received timolol, 1 mg iv, or matching placebo as a starting dose, followed by a second and third dose of 1 mg each (or matching placebo) at 20-min intervals if the arrhythmia did not convert to sinus rhythm. Subjects in whom the sinus rhythm returned or the ventricular rate decreased to less than 100 bpm were transferred to a dosing regimen of timolol in 10-mg tablets twice a day by mouth, 1 hr after the last intravenous dose. Data indicated that the mean decrease in heart rate was 44 bpm after timolol and 7 bpm after placebo. The overall proportion of responders (either conversion to sinus rhythm or a decrease in ventricular rate to less than 100 bpm) was 68% after timolol and 7% after placebo. The proportions of responders after timolol were significantly higher than the proportions after placebo for paroxysmal supraventricular tachycardia (26 of 32 subjects and two of 38 subjects), atrial fibrillation (17 of 29 subjects and three of 32 subjects), and atrial flutter (seven of 11 subjects and one of nine subjects). The most common adverse effects were bradycardia and hypotension.
Asunto(s)
Arritmias Cardíacas/tratamiento farmacológico , Timolol/administración & dosificación , Adolescente , Adulto , Anciano , Ensayos Clínicos como Asunto , Método Doble Ciego , Femenino , Atrios Cardíacos , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Distribución Aleatoria , Timolol/efectos adversos , Timolol/uso terapéuticoRESUMEN
The antihypertensive effect of enalapril maleate, a new converting enzyme inhibitor, was evaluated in a multiclinic, double-blind, randomized study in patients with mild to moderate essential hypertension. The analyses were done in two ways, with patients who violated the entry criteria of the protocol excluded, and according to the intention to treat principle. Enalapril in dosages of 10 to 40 mg daily administered alone or concomitantly with hydrochlorothiazide was compared to propranolol (80 to 240 mg daily) alone or concomitantly with the diuretic. The study showed that enalapril significantly lowered both systolic and diastolic blood pressure. At each timepoint measured in the course of 26 weeks of therapy, the patients in the enalapril group consistently had greater decreases in blood pressure than patients in the propranolol group although not always significantly. The enalapril treatment group had a decrease in the mean arterial blood pressure of 22.2 mmHg compared to the propranolol group of 17.9 mmHg at the end of the study. These results were similarly independent of the way the data were analyzed. Fewer patients in the enalapril group required the addition of hydrochlorothiazide to maintain optimal control of blood pressure. Enalapril was found to be safe and well tolerated over the long-term of 48 weeks. Side effects such as leukopenia and taste perversions believed to be sulfhydryl-related were not encountered. The occurrence of rash and proteinuria was rare. Thiazide-induced hypokalemia, hyperuricemia and hyperglycemia appeared to be attenuated by enalapril. The favorable efficacy and side-effect profile provide the basis for enalapril to be a drug of choice when initiating antihypertensive therapy.