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 (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.
Department of Medicine A, Assaf Harofeh Medical Center, Zerifin, Israel.
R
R
Zaidenstein
V
V
Dishi
M
M
Gips
S
S
Soback
N
N
Cohen
J
J
Weissgarten
A
A
Blatt
A
A
Golik
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D001628:Beverages; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D002957:Citrus; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D014700:Verapamil / Q000097:blood / Q000493:pharmacokinetics*
D002121:Calcium Channel Blockers; D014700:Verapamil