EFFECT OF GRAPEFRUIT JUICE ON DRUG-METABOLISM IN RATS

The effect of grapefruit juice on in vivo drug metabolism was investig ated 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, pent obarbitone sleeping time and the tremorgenic action of tremorine was s tudied. 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 in creases in pentobarbitone sleeping time that reached 46 and 79%, respe ctively, compared with 107% produced by cimetidine (50 mg/kg, ip). The juice at 4 ml/kg also significantly increased plasma theophylline con centration when measured 15, 30, 60 and 90 min after ip theophylline a dministration (10 mg/kg). Thereafter, no significant differences were detected in plasma drug concentrations between juice- and saline-treat ed animals. Administration of tremorine (25 mg/kg, ip) to saline-treat ed controls produced, within 2 or 3 min, tremors, piloerection, profus e salivation, defaecation, urination and chromodacryorrhesis (red tear s). 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 cimet idine-treated rats. These results suggest that grapefruit juice may ac t as an inhibitor of drug metabolism in rats, and that its consumption may alter the disposition of certain concomitantly administered drugs .