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Orange juice substantially reduces the bioavailability of the β‐adrenergic–blocking agent celiprolol
Author(s) -
Lilja Jari J.,
JunttiPatinen Laura,
Neuvonen Pertti J.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.002
Subject(s) - celiprolol , orange juice , bioavailability , chemistry , ingestion , crossover study , orange (colour) , pharmacokinetics , excretion , pharmacology , zoology , endocrinology , medicine , food science , heart rate , biochemistry , blood pressure , biology , placebo , alternative medicine , pathology
Background Grapefruit juice was recently found to decrease plasma concentrations of the β‐adrenergic receptor–blocking agent celiprolol. Our objective was to investigate the effect of orange juice on the pharmacokinetics of celiprolol in healthy subjects. Methods In a randomized crossover study with 2 phases and a washout of 2 weeks, 10 healthy volunteers ingested either 200 mL normal‐strength orange juice or water 3 times a day for 2 days. On the morning of day 3, 1 hour after ingestion of 200 mL orange juice or water, each subject ingested 100 mg celiprolol with either 200 mL orange juice or water. In addition, 200 mL orange juice or water was ingested at 4, 10, 22, and 27 hours after celiprolol intake. The concentrations of celiprolol in plasma and its excretion into urine were measured up to 33 hours after its dosing. Systolic and diastolic blood pressures and heart rate were recorded up to 10 hours. Results Orange juice reduced the mean peak plasma concentration of celiprolol by 89% ( P < .01) and the mean area under the plasma celiprolol concentration–time curve by 83% ( P < .01). The time to peak concentration of celiprolol increased from 4 to 6 hours ( P < .05), and the half‐life was prolonged from 4.6 to 10.8 hours ( P = .05) after ingestion of orange juice. Orange juice reduced the urinary excretion of celiprolol by 77% ( P < .01). No significant differences were observed in the hemodynamic variables between the phases. Conclusions Orange juice substantially reduces the bioavailability of celiprolol, but the mechanism of this interaction remains to be resolved. For example, modulation of intestinal pH and of function of transporters implicated in the absorption of celiprolol may be involved. Because of the great extent of the orange juice–celiprolol interaction and a wide use of orange juice, this interaction is likely to have clinical importance in some patients, although hemodynamic consequences were not seen in young healthy subjects. Clinical Pharmacology & Therapeutics (2004) 75 , 184–190; doi: 10.1016/j.clpt.2003.11.002