Rectal pharmacokinetics of budesonide

Abstract

The pharmacokinetics and systemic availability of budesonide after rectal administration of two single enema doses (2 mg in 100 ml fluid of almost identical composition) were compared in 15 healthy volunteers. In 11 of these subjects, 2 mg oral budesonide in a gelatine capsule was given on a separate occasion. An intravenous administration (0.5 mg) was given as reference. With this design, individual hepatic bypass of the rectally administered budesonide dose could be estimated. The pharmacokinetics of the two enema formulations were similar, although not bioequivalent. Mean systemic availability was 16% (range 4.2-43%) and 15% (3.2-50%) after rectal administration and 6.3% (2.4-10%) after oral administration. The rectal data revealed a small intra- but a substantial inter-subject variability in systemic availability. Cmax was 3.3 nmol center dot l-1 (0.95-8.2), 3.0 nmol center dot l-1 (0.64%-8.9) and 1.3 nmol center dot l-1 (0.61-3.0), respectively, for the three formulations. Absorption was rapid and essentially terminated within 3 h after rectal dosing [tmax = 1.3 h for both formulations (range 0.5-2.0)], but was slower after oral dosing [tmax = 2.1 h (1.0-6.0)]. If a complete absorption after oral and rectal dosing is assumed, the fraction of the rectal dose entering the liver at first pass can be calculated to be 88% (55-99%). The higher systemic availability and intersubject variability after rectal dosing does not seem to be caused by differences in first-pass liver metabolism but rather by hepatic bypass of a varying portion of administered drug. This portion seems to be typical for an individual and might be explained by anatomical differences between subjects.

Single‐Dose and Steady‐State Pharmacokinetic and Pharmacodynamic Evaluation of Therapeutically Clinically Equivalent Doses of Inhaled Fluticasone Propionate and Budesonide, Given as Diskus® or Turbohaler® Dry‐Powder Inhalers to Healthy Subjects

“…While the systemic clearance of BUD and FP is similar, BUD shows a somewhat higher oral bioavailability than FP. [1][2][3][4] Reports also indicate that the pulmonary deposition of BUD given by Turbohaler ® is higher than that for FP given as Diskus ® . 20,25 Several methods are currently used to assess the effect of inhaled corticosteroids on the HPA axis function.…”

A comparison of the efficacy and safety of inhaled corticosteroids in asthma

“…This has some validity for BDP, which has a relatively low inactivation by first-pass metabolism (19,40), but it has less validity for BUD and FI? The systemic bioavailability of BUD after oral dosing is 6-13% as most of the GI dose is inactivated by first-pass metabolism (41,42). Fluticasone has been calculated to have a systemic bioavailability of less than 1% after oral dosing (25,26).…”

Bioavailability profile of Uceris MMX extended-release tablets compared with Entocort EC capsules in healthy volunteers

“…4 As a consequence, budesonide has only modest effects on the hypothalamic-pituitary-adrenal axis. 6,7 As an example, a rectally-administered budesonide enema was found to have comparable efficacy to a rectally-administered prednisolone enema in UC, but was associated with significantly less plasma cortisol suppression. 8 Oral budesonide, administered as a plain formulation, is completely absorbed high in the gastrointestinal (GI) tract, making this formulation unsuitable for the treatment of UC, which requires delivery of active drug distally to the entire colon for optimal therapeutic effect.…”