Apple juice greatly reduces systemic exposure to atenolol

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT •Atenolol is an antihypertensive drug, of which negligible amounts are metabolized. •Fruit juices may decrease the oral absorption of drugs by inhibiting intestinal drug transporters, as demonstrated in vitro and in vivo. WHAT THIS STUDY ADDS •The pharmacokinetic characteristics of atenolol were determined according to the SLCO2B1 genotype after apple juice administration in healthy Korean volunteers. •Apple juice ingestion markedly reduced the systemic exposure to atenolol, but genetic variations in SLCO2B1 were unlikely to contribute substantial variability to the pharmacokinetics of atenolol. AIM Fruit juice reduces the plasma concentrations of several β-adrenoceptor blockers, likely by inhibiting OATP2B1-mediated intestinal absorption. The aim of this study was to investigate the effects of apple juice on the pharmacokinetics of atenolol. METHODS Twelve healthy Korean volunteers with genotypes of SLCO2B1 c.1457C> T (*1/*1 (n= 6) and *3/*3 (n= 6)) were enrolled in this study. In a three-phase, one-sequence crossover study, the pharmacokinetics (PK) of atenolol was evaluated after administration of 50mg atenolol. Subjects received atenolol with either 300ml water, 1200ml apple juice or 600ml apple juice. RESULTS Apple juice markedly reduced the systemic exposure to atenolol. The geometric mean ratios (95% confidence intervals) of apple juice:water were 0.18 (0.13, 0.25, 1200ml) and 0.42 (0.30, 0.59, 600ml) for the AUC(0,t_last). In this study, the PK parameters of atenolol responded in a dose-dependent manner to apple juice. CONCLUSIONS Apple juice markedly reduced systemic exposure to atenolol. The genetic variation of SLCO2B1 c.1457C>T had a minimal effect on the pharmacokinetics of atenolol when the drug was administered with water or apple juice.