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A Dose-Escalation Study Demonstrates the Safety and Tolerability of Cellobiose in Healthy Subjects.

ABSTRACT: The disaccharide and innovative ingredient cellobiose, consisting of two ?-glucose molecules linked by a ?(1?4) bond is the main component of cellulose. Cellobiose can be used within a wide variety of foodstuffs and functional foods as a low-caloric bulking agent or as a substitute for lactose. For purposes of industrial large-scale production, cellobiose is produced by an enzymatic reaction in which sucrose and glucose are converted to cellobiose and fructose. The goal of this single-arm, dose-escalation study was to evaluate the safety and tolerability of cellobiose and to determine the maximum tolerated dose of cellobiose in healthy subjects. Following a baseline period, consecutive cohorts of six subjects each consumed either single doses of 10, 15, 20 and 25 g, while 12 subjects each received multiple doses of 15 g or 20 g cellobiose (twice daily, 14 days). The main recorded parameters were stool consistency, gastrointestinal well-being (Gastrointestinal Symptom Rating Scale) and adverse events. In each highest single/multiple dosage group, some sensitive subjects experienced flatulence, borborygmus and/or transient diarrhoea. A 100% global tolerability rating makes 20 g cellobiose a tolerable dose for single use. For repeated consumption, we propose up to 15 g cellobiose twice daily (92.6% global tolerability rating). Cellobiose is a promising new ingredient with excellent tolerability.

SUBMITTER: More MI

PROVIDER: S-EPMC7019479 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Project description:AIMS:To characterize the pharmacokinetics, pharmacodynamics and safety of esaxerenone, a mineralocorticoid receptor antagonist, in healthy adult Japanese men. METHODS:Double-blind, placebo-controlled, sequential, dose-escalation studies were conducted in subjects randomized to receive oral once-daily esaxerenone (ranges: 5-200 mg [single-dose]; 10-100 mg over 10 days [multiple-dose]) or placebo under fasting conditions. Plasma concentrations were analysed by liquid chromatograph-tandem mass spectrometry. Pharmacokinetic parameters were determined by noncompartment analysis. Plasma/urine levels of pharmacodynamic biomarkers for mineralocorticoid receptor activity were evaluated. RESULTS:In total, 48/48 and 39/40 subjects completed the single- and multiple-dose studies, respectively. Exposures were generally dose-proportional. The tmax , t1/2 and CL/F remained unchanged, independent of dose; the respective ranges were 1.5-4.0 h, 22.3-25.1 h, and 4.0-5.2 l h-1 (multiple-dose study). Vz /F ranged from 136.5 to 283.7 l in the multiple-dose study, and exposure reached steady state by day 4. The mean observed accumulation ratio, by dose, ranged from 1.36-1.98. The urinary Na+ /K+ ratio increased after single-dose administration; however, its relationship to the doses tested remains unclear. Plasma renin activity, active renin concentration and aldosterone concentration increased dose-dependently. Although blood potassium levels increased dose-dependently in the multiple-dose study (reaching a maximum mean ± standard deviation of 4.63 ± 0.354 mmol l-1 in the 100-mg group), no safety/tolerability-related problems were detected in either study. CONCLUSIONS:Exposure levels in healthy adults receiving esaxerenone were generally dose-proportional. Dose-dependent changes in plasma pharmacodynamic biomarkers for the mineralocorticoid receptor were identified during multiple-dose treatment and support the pharmacological activity of esaxerenone. No important safety concerns were identified.

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A Dose-Escalation Study Demonstrates the Safety and Tolerability of Cellobiose in Healthy Subjects.

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