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The effect of grapefruit juice on the pharmacokinetics of orally administered verapamil
R Zaidenstein1, V Dishi, M Gips
1Department of Medicine A, Assaf Harofeh Medical Center, Zerifin, Israel.
Objective:
To investigate the effect of grapefruit juice (GJ) on the pharmacokinetics of orally administered verapamil in hypertensive patients.
Methods:
Ten hypertensive patients on chronic verapamil treatment participated in a two-day study. On day 1 200 ml of water was given 1 hour before, and together with the morning verapamil dose; on the day 2, water was replaced by GJ in the same order. Serial blood samples were collected and the concentrations of verapamil and its main dealkylated metabolite (D-617) were determined by high-performance liquid chromatography (HPLC). The area under the concentration versus time curve of verapamil (AUCv) and its metabolite D-617 (AUCM) were calculated before and after GJ ingestion. The peak serum concentration (Cmax) and the time until its appearance (tmax) were also determined.
Results:
GJ did not affect Cmax, tmax, AUCv or AUVm. The AUCv/AUCm ratio (AUCR) was slightly, but significantly, increased after GJ (1.67 vs 1.92).
Conclusions:
A single administration of GJ with short-acting verapamil has no significant effect on the pharmacokinetics, of verapamil.