ABSTRACT
Grapefruit juice (GFJ) inhibits CYP3A activity in the gut wall, thereby decreasing first-pass metabolism of CYP3A substrates. In this study be evaluated the influence of GFJ on the systemic availability of budesonide, a CYP3A-metabolised drug, both from an extended-release (ER) formulation and plain capsules. Eight healthy men participated in this open crossover study. Three mg budesonide as ER capsules or plain capsules was swallowed with or without previous intake of GFJ. Regular-strength GFJ 200 ml was given three times a day for four days. Budesonide was administered immediately after the first intake on the fourth day. A simultaneous intravenous low dose of deuterium-labelled budesonide enabled estimation of bioavailability and absence of hepatic inhibition. Concentrations of labelled and unlabelled budesonide in plasma were measured. GFJ did not affect systemic clearance of budesonide. Although absorption of the ER formulation to a great extent occurs from ileum and proximal colon where CYP3A activity is lower than in the upper small intestine, GFJ about doubled bioavailability after both ER and plain capsules. In conclusion, regular intake of grapefruit juice doubled the bioavailability of both plain and delayed-release budesonide, probably because of inhibition of all mucosal CYP3A activity.