, Volume 43, Issue 12, pp 803-821
Date: 30 Sep 2012

Pharmacokinetics of Budesonide (Entocort™ EC) Capsules for Crohn’s Disease

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Abstract

This overview summarises available pharmacokinetic data on budesonide capsules (Entocort™ EC), approved for the treatment of mild-to-moderate active Crohn’s disease involving the ileum and/or ascending colon and for prolongation of symptom control. Budesonide is a locally-acting glucocorticosteroid with an extensive, primarily hepatic, metabolism after oral administration. It is rapidly absorbed and biotransformed by cytochrome P450 (CYP) 3A to metabolites with negligible glucocorticoid activity.

Entocort™ EC, a pH- and time-dependent oral formulation of budesonide, was developed to optimise drug delivery to the ileum and throughout the colon. Pharmaco-scintigraphic studies have confirmed that the Entocort™ EC formulation delays budesonide absorption and prolongs the rate of elimination but maintains complete absorption. This improves the delivery of budesonide to the intestinal lumen relative to a plain formulation. A low systemic availability of 9–21% indicates extensive first-pass elimination. Food appears to have little impact on the absorption of budesonide from Entocort™ EC capsules and the pharmacokinetics are dose-proportional between 3 and 15mg. On average, systemic availability was 2.5-fold higher in patients with cirrhosis compared with healthy controls; however, mild liver impairment had little effect on systemic exposure. Pharmacokinetics appear unaffected by gender and age, although this has not been tested in younger children. Renal impairment is not expected to have an impact on the kinetics of Entocort™ EC.

Budesonide is unlikely to inhibit the metabolism of other drugs, including CYP3A4 substrates, mainly because of the very low plasma concentrations obtained with the compound even after high doses of Entocort™ EC capsules. Strong CYP3A4 inhibitors, such as ketoconazole, will inhibit the metabolism of budesonide, resulting in several-fold increases in the area under the concentration-time curve of budesonide. Also, grapefruit juice intake may increase systemic availability of budesonide, probably by inhibition of intestinal CYP3A4 activity. Unlike prednisolone, oral contraceptives do not alter plasma budesonide concentrations. An increased pH obtained by gastric acid inhibitory drugs, such as omeprazole, does not affect the pharmacokinetics of budesonide.

In summary, budesonide capsules (Entocort™ EC) possess many pharmacological features that make the formulation well adapted for a targeted treatment of inflammatory disorders, such as Crohn’s disease involving the ileum and ascending colon.