Effect of grapefruit juice on drug metabolism in rats.
The effect of grapefruit juice on in vivo drug metabolism was investigated in rats. The juice (4 ml or 8 ml/kg) was given orally once daily for 2 consecutive days and its effect on theophylline metabolism, pentobarbitone sleeping time and the tremorgenic action of tremorine was studied. The effect of grapefruit juice on some of these parameters was compared with that of the known drug metabolism inhibitor cimetidine given ip. Grapefruit juice at 4 ml and 8 ml/kg produced significant increases in pentobarbitone sleeping time that reached 46 and 79%, respectively, compared with 107% produced by cimetidine (50 mg/kg, ip). The juice at 4 ml/kg also significantly increased plasma theophylline concentration when measured 15, 30, 60 and 90 min after ip theophylline administration (10 mg/kg). Thereafter, no significant differences were detected in plasma drug concentrations between juice- and saline-treated animals. Administration of tremorine (25 mg/kg, ip) to saline-treated controls produced, within 2 or 3 min, tremors, piloerection, profuse salivation, defaecation, urination and chromodacryorrhesis (red tears). The onset of appearance of these signs was delayed to about 7 min in rats pretreated 1 hr earlier with either grapefruit juice (4 ml/kg, orally) or cimetidine (50 mg/kg, ip). The severity of the above signs was markedly reduced to a similar extent in both the juice- and cimetidine-treated rats. These results suggest that grapefruit juice may act as an inhibitor of drug metabolism in rats, and that its consumption may alter the disposition of certain concomitantly administered drugs.[1]References
- Effect of grapefruit juice on drug metabolism in rats. Sharif, S.I., Ali, B.H. Food Chem. Toxicol. (1994) [Pubmed]
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