The effect of grapefruit juice on the pharmacokinetics of orally administered verapamil

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 (AUC(v)) and its metabolite D-617 (AUC(M)) were calculated before and after GJ ingestion. The peak serum concentration (C(max)) and the time until its appearance (t(max)) were also determined. Results: GJ did not affect C(max) t(max) AUC(v) or AUV(m). The AUC(v)/AUC(m) ratio (AUC(R)) 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.