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Pomegranate Juice Does Not Impair Clearance of Oral or Intravenous Midazolam, a Probe for Cytochrome P450‐3A Activity: Comparison With Grapefruit Juice
Author(s) -
Farkas Dora,
Oleson Lauren E.,
Zhao Yanli,
Harmatz Jerold S.,
Zinny Miguel A.,
Court Michael H.,
Greenblatt David J.
Publication year - 2007
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006298359
Subject(s) - grapefruit juice , midazolam , chemistry , cyp3a , triazolam , pharmacology , volunteer , oral administration , pharmacokinetics , volume of distribution , citrus paradisi , cytochrome p450 , metabolism , benzodiazepine , medicine , biochemistry , biology , sedation , receptor , rutaceae , horticulture , agronomy
The effect of pomegranate juice (PJ) or grapefruit juice (GFJ) on CYP3A activity was studied in vitro and in healthy human volunteers. In human liver microsomes, the mean 50% inhibitory concentrations (IC 50 ) for PJ and GFJ versus CYP3A (triazolam α‐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.