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Effects of orange juice on the pharmacokinetics of atenolol.

Author(s): Lilja JJ, Raaska K, Neuvonen PJ

Affiliation(s): Department of Clinical Pharmacology, University of Helsinki, Helsinki University Central Hospital, Haartmaninkatu 4, 00290, Helsinki, Finland. jari.lilja@hus.fi

Publication date & source: 2005-07, Eur J Clin Pharmacol., 61(5-6):337-40. Epub 2005 Jun 28.

Publication type: Randomized Controlled Trial

OBJECTIVE: Fruit juices can significantly change the pharmacokinetics of several drugs. Our objective was to investigate the effect of orange juice on the pharmacokinetics of the beta-blocking agent atenolol. METHODS: In a randomized cross-over study with two phases and a washout of 2 weeks, ten healthy volunteers took either 200 ml orange juice or water thrice daily for 3 days and twice on the fourth day. On the morning of day 3, each subject ingested 50 mg atenolol with an additional amount of either 200 ml orange juice or water. The plasma concentrations of atenolol and the cumulative excretion of atenolol into urine were measured up to 33 h after its dosing. Systolic and diastolic blood pressures and heart rate were recorded in a sitting position before the intake of atenolol and 2, 4, 6, and 10 h after. RESULTS: Orange juice decreased the mean peak plasma concentration (C(max)) of atenolol by 49% (range 16-59%, P<0.01), and the mean area under the plasma atenolol concentration-time curve (AUC(0-33 h)) by 40% (range 25-55%, P<0.01). The time of the peak concentration (t(max)) and the elimination half-life (t(1/2)) of atenolol remained unchanged by orange juice. The amount of atenolol excreted into urine was decreased by 38% (range 17-60%, P<0.01), but the renal clearance remained unaltered. The average heart rate was slightly higher during the orange juice+atenolol phase than during the water+atenolol phase. CONCLUSIONS: Orange juice moderately interferes with the gastrointestinal absorption of atenolol. This food-drug interaction can be of clinical significance.

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