Celiprolol Orange juice

In a more recent work, GFJ and orange juice have been reported to reduce the availability of fexofenadine and celiprolol (22,76,107). Both drugs are substrates for P-gp and OATP, but not CYP3A4 (108,109). If P-gp had played a major role in the observed interactions, the bioavailability would have been increased instead of decreased. This led to the conclusion that a mechanism other than P-gp was involved. In theory, the inhibition of OATP could lead to a decreased absorption of OATP substrates into intestinal enterocytes. This hypothesis was tested by several in vitro studies. 

Lilja JJ, Juntti-Patinen L, Neuvonen PJ. Orange juice substantially reduces the bioavailability of the beta-adrenergic-blocking agent celiprolol. Clin Pharmacol Ther 2004 75(3) 184-190. 

In terms of ADMET, the absorption of celiprolol from the gastrointestinal tract is rapid, and its time to onset of action is only 30-60 min, with a peak effect in about 2-3 h. The presence of food in the gut can reduce absorption by about 30%. Itraconazole increases, while grapefruit juice significantly decreases, plasma concentrations of celiprolol [138]. Likewise, orange juice substantially reduces the bioavailability of celiprolol, and because it is consumed widely, this interaction is like-... 

The bioavailability of celiprolol is markedly reduced by both grapefruit juice and orange juice, the bioavailability of atenolol is moderately reduced by orange juice, and the bioavailability of ta-linolol is reduced by grapefruit juice. 

The mechanism of this effect is not known, but suggestions include an effect on intraduodenal pH and the lipid solubility of celiprolol, or the formation of a complex between celiprolol and an ingredient of grapefruit or orange juice that interfered with celiprolol absorption. Alternatively, inhibition of uptake transporter proteins in the intestine may have reduced absorption. ... 

Although the clinical relevance of these effects has not been fully assessed, the studies suggest that the effects of celiprolol on blood pressure and heart rate are not affected. Nevertheless the marked reduction in celiprolol bioavailability in the presence of grapefruit or orange juice suggests this interaction may of clinical significance in some patients. ... 

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