OBJECTIVES: Our objective was to assess the importance of @entity69636 in drug interactions through comparisons between grapefruit juice and lime juice and the potential for drug interactions with red wine. METHODS: Bergamottin content and in vitro reversible/irreversible inhibition of cytochrome P450 (CYP) 3A4 monooxygenase activities were determined for grapefruit and lime juices. The oral pharmacokinetics of @entity10202 and its primary metabolite ( @entity69637 ) were determined with 250 mL of grapefruit juice, one quarter-strength lime juice, red wine, or water in a randomized crossover study. RESULTS: Bergamottin concentrations in grapefruit and lime juices were 25 and 100 micromol/L, respectively. For reversible inhibition, log volume-residual @entity5322 activity relationships for grapefruit and lime juices had negative linear slopes that were parallel. The curve for grapefruit juice was 4.0-fold right-shifted, as compared with that for lime juice. For irreversible inhibition, the curves for grapefruit and lime juices were 4.0- and 1.4-fold left-shifted, as compared with those for reversible inhibition, respectively. Grapefruit juice increased the mean @entity10202 area under the plasma concentration-time curve (AUC) (mean +/- SE, 55 +/- 9 nmol. h/L versus 29 +/- 6 nmol. h/L; P <.05) and the plasma peak drug concentration (16 +/- 3 nmol/L versus 8 +/- 2 nmol/L, P <.05) and decreased the @entity69637 / @entity10202 AUC ratio compared with those of water. One quarter-strength lime juice did not alter mean values. However, the changes in individual @entity10202 AUC after grapefruit juice and lime juice correlated (r(2) = 0.95) with a low slope (0.36). One quarter-strength lime juice more than doubled @entity10202 AUC and plasma peak drug concentration in 2 subjects. Red wine prolonged mean @entity10202 time to plasma peak drug concentration. @entity10202 concentrations were low and peaked abruptly in 4 subjects. Adverse effects occurred in 1 subject. CONCLUSIONS: Bergamottin and reversible inhibition are not the primary substance and mechanism responsible for inhibition of @entity5322 activity clinically. Red wine can cause dose dumping of extended-release @entity10202 in certain individuals.

XXXX , lime juice, and red wine as inhibitors of cytochrome P450 3A4 activity: comparison with grapefruit juice.

@entity5322 :: ('1576', 'Gene') :: ['CYP3A4'] @entity10202 :: ('MESH:D015736', 'Chemical') :: ['Felodipine', 'felodipine'] @entity69637 :: ('MESH:C081790', 'Chemical') :: ['dehydrofelodipine'] @entity69636 :: ('MESH:C068337', 'Chemical') :: ['bergamottin']
@entity69636 :: (MESH:C068337,Chemical) :: ['Bergamottin']
