The effects of grapefruit juice on the pharmacokinetics of erythromycin.
OBJECTIVE
To study the effects of grapefruit juice on the pharmacokinetics of erythromycin.


METHODS
The effects of grapefruit juice intake on the pharmacokinetics of erythromycin were investigated in six healthy male volunteers, who received 400 mg erythromycin with either water or grapefruit juice. The measurement of erythromycin in plasma samples were achieved by simple Sep-Pak CN cartridge extraction coupled with the electrochemical determination HPLC method, which was developed for the determination of erythromycin in human plasma in the present study.


RESULTS
Grapefruit juice, compared with water intake, significantly (P<0.05) increased the mean Cmax value (1.65+/-0.94 versus 2.51+/-0.68 microg/ml) and the mean AUC0-12 value of erythromycin (5.92+/-3.25 versus 8.80+/-1.32microg.h/ml). However, the Tmax and t1/2 values of erythromycin were not affected by grapefruit juice intake.


CONCLUSIONS
These results indicate that the bioavailability of erythromycin was increased by the inhibitory effect of grapefruit juice on cytochrome P450 (CYP) 3A4-mediated metabolism in the small intestine.
Kanazawa
S
S
Department of Pharmacy, Hirosaki University Hospital, Japan.
Ohkubo
T
T
Sugawara
K
K
D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001628:Beverages; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D002957:Citrus; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004917:Erythromycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D004917:Erythromycin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A