Journal of clinical pharmacology · 2024
Effect of Food on the Pharmacokinetics, Safety, and Tolerability of Budesonide Oral Suspension in Healthy Adult Participants: A Randomized Phase 1 Study.
СтатьяРандомизированное исследованиеКлиническое исследование I фазыПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Prokopienko Alexander J, Wang Junyao, Yajnik Vijay, Baratta Mike, Desai Nirav K, Richmond Camilla A, Suri Ajit
Аннотация
Budesonide oral suspension (BOS) is a swallowed corticosteroid indicated for 12-week therapy in eosinophilic esophagitis with minimal systemic exposure following administration. We aimed to assess the relative bioavailability of a single dose of BOS administered under fasting and fed (high-fat/high-calorie meal) conditions. Healthy adult volunteers (N = 20) were enrolled in an open-label, single-center, crossover study and were randomized (1:1) to receive a single oral dose of BOS 2.0 mg under fasting or fed conditions, with a 48-h washout period before crossover to the alternative conditions. Serial plasma samples were collected before and up to 24 h after dosing. Pharmacokinetic (PK) parameters were calculated from plasma budesonide concentration-time profiles by noncompartmental analysis. The mean peak budesonide concentration (Cmax) was ∼13% lower under fed than under fasting conditions (604.1 vs 692.9 pg/mL). Areas under the concentration-time curves from dosing to the last measurable budesonide concentration and from dosing to infinity were ∼26% higher and ∼27% higher under fed than fasting conditions (3529 vs 2811 pg h/mL and 3892 vs 3075 pg h/mL, respectively). The median time to peak plasma budesonide concentration was significantly longer (∼1 h) under fed than fasting conditions (2.516 vs 1.286 h, P < .001). Safety and tolerability were also assessed throughout the study; all adverse events were mild or moderate in severity. Despite slight differences in budesonide PK parameters between fed and fasting conditions, the effect of food on systemic exposure to budesonide (BOS formulation) is not expected to be clinically meaningful.