The effects of grapefruit juice on the pharmacokinetics of erythromycin

Abstract

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 C_max value (1.65±0.94 versus 2.51±0.68µg/ml) and the mean AUC_0–12 value of erythromycin (5.92±3.25 versus 8.80±1.32µg·h/ml). However, the T_max and t_1/2 values of erythromycin were not affected by grapefruit juice intake. Conclusion: 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.