RESUMEN
BACKGROUND: Olestra is a nonabsorbable, energy-free fat substitute. Because it is not absorbed, it may cause digestive symptoms when consumed in large amounts. OBJECTIVE: To compare the frequency and impact of gastrointestinal symptoms in adults and children who freely consume snacks containing olestra or regular snacks in the home. DESIGN: 6-week, double-blind, randomized, parallel, placebo-controlled trial. SETTING: General community. PARTICIPANTS: 3181 volunteers 2 to 89 years of age. INTERVENTION: Households received identical packages labeled as containing olestra corn or potato chips. These packages contained either olestra or regular chips (control). MEASUREMENT: Gastrointestinal symptoms and their impact on daily activities were reported in a daily record. RESULTS: At least one gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points [95% CI, -3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did not differ significantly in the proportion of participants who reported individual gastrointestinal symptoms; however, more controls reported nausea (8.4% compared with 5.7%; difference, -2.7 percentage points [CI, -4.9 to -0.4 percentage points]; P = 0.02). The only difference between groups for the mean numbers of days on which symptoms were reported was that participants in the olestra group had 1 more symptom-day of more frequent bowel movements than did controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9 symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ in the impact of symptoms on daily activities. CONCLUSIONS: Clinically meaningful or bothersome gastrointestinal effects are not associated with unregulated consumption of olestra corn and potato chips in the home.
Asunto(s)
Grasas Insaturadas en la Dieta/efectos adversos , Sustitutos de Grasa/efectos adversos , Ácidos Grasos/efectos adversos , Alimentos , Enfermedades Gastrointestinales/etiología , Sacarosa/análogos & derivados , Triglicéridos/efectos adversos , Dolor Abdominal/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Estreñimiento/etiología , Diarrea/etiología , Registros de Dieta , Método Doble Ciego , Humanos , Lactante , Náusea/etiología , Efecto Placebo , Sacarosa/efectos adversosRESUMEN
STUDY OBJECTIVES: To investigate the use of in vitro and in vivo data in the development of a sustained-release, carbomer-based dosage form (Entex LA tablets); and to compare the in vitro dissolution of pseudoephedrine from a sustained-release, hydroxypropylcellulose-based dosage form (Entex PSE tablets) and four branded competitors with different sustained-release matrixes. DESIGN: Entex LA: In vitro testing by rotating bottle method and in vivo testing as double-blind, randomized, crossover, 24-hour study. Entex PSE and four competitors: in vitro testing by paddle method. SETTING: A pharmaceutical research and development facility. PATIENTS: Fifteen health, adult, volunteer Caucasian men between ages 18 and 40 years. MAIN RESULTS: Three formulations of Entex LA, varying in carbomer content by 3-5%, were studied. As carbomer content increased, in vitro dissolution rate directionally decreased. Plasma concentrations of active ingredients guaifenesin and phenylpropanolamine were also slightly although directionally decreased. The in vitro method was sensitive to small changes in carbomer content. Larger changes in carbomer content would be required to establish an in vitro-in vivo correlation. The in vitro comparison of Entex PSE and four similar branded products showed important differences in dissolution profiles. The mean cumulative release of pseudoephedrine from Entex PSE was 39% at 1.5 hours, 62% at 4.0 hours, and 80% at 8.0 hours. The other products released pseudoephedrine more rapidly, with the two fastest-dissolving products releasing 61-62% in the first 1.5 hours. CONCLUSIONS: Sustained-release, polymer-based dosage forms such as Entex LA and Entex PSE can be complex and pose special challenges in design, development, and reformulation. For Entex LA, changes in polymer concentration and dye system influenced the in vitro (dissolution) performance. In vivo (plasma) data helped establish a defined range in which carbomer concentration could be varied to achieve the best manufacturing performance without affecting product performance. For Entex PSE and four branded competitor products, the cumulative in vitro release (dissolution) of pseudoephedrine varied widely. Release from Entex PSE was more consistent and more gradual than that from some of the comparison products. Because the absorption rate of the active ingredients pseudoephedrine and gauifenesin is governed by the dissolution rate, the observed differences suggest that the products tested may differ in biologic performance. Although in vitro dissolution data may not necessarily correlate with in vivo differences in clinical safety or efficacy, the potential for unexpected product performance may be signaled by inconsistent in vitro dissolution characteristics, especially for sustained-release dosage forms.