J Clin Pharmacol. 2007 Mar;47(3):286-94.
Pomegranate juice does not impair clearance of oral or intravenous midazolam, a
probe for cytochrome P450-3A activity: comparison with grapefruit juice.
Farkas D, Oleson LE, Zhao Y, Harmatz JS, Zinny MA, Court MH, Greenblatt DJ.
of Pharmacology and Experimental Therapeutics, Tufts University School
of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
The effect of pomegranate juice (PJ) or grapefruit juice (GFJ) on CYP3A
activity was studied in vitro and in healthy human volunteers.
liver microsomes, the mean 50% inhibitory concentrations (IC(50)) for
PJ and GFJ versus CYP3A (triazolam alpha-hydroxylation) were 0.61% and
0.55%, (v/v) respectively, without preincubation of inhibitor with
microsomes. After preincubation, the IC(50) for PJ increased to 0.97%
(P < .05), whereas the IC(50) for GFJ decreased to 0.41% (P <
.05), suggesting mechanism-based inhibition by GFJ but not PJ.
Pretreatment of volunteer subjects (n = 13) with PJ (8 oz) did not
alter the elimination half-life, volume of distribution, or clearance
of intravenous midazolam (2 mg). Administration of PJ also did not
affect C(max), total area under the curve (AUC), or clearance of oral
midazolam (6 mg). However, GFJ (8 oz) increased midazolam C(max) and
AUC by a factor of 1.3 and 1.5, respectively, and reduced oral
clearance to 72% of control values. Thus, PJ does not alter clearance
of intravenous or oral midazolam, whereas GFJ impairs clearance and
elevates plasma levels of oral midazolam.