Effects of repeated ingestion of grapefruit juice on the single and multiple oral-dose pharmacokinetics and pharmacodynamics of alprazolam

The effects of repeated ingestion of grapefruit juice, an inhibitor of cyto chrome P-450 3A4 (CYP3A4), on the pharmacokinetics and pharmacodynamics of both single and multiple oral doses of alprazolam, a substrate of CYP3A4. w ere examined. In study 1, eight healthy volunteers ingesting 600 ml/day wat er or grapefruit juice for 10 days took a single oral 0.8-mg dose of alpraz olam on the eighth day. Plasma drug concentrations were monitored up to 48 h after alprazolam dosing together with evaluation of psychomotor function. Grapefruit juice altered neither the plasma concentrations of alprazolam a t any time points, any pharmacokinetic parameters, nor the majority of psyc homotor function parameters in subjects. In study 2, 11 patients with anxie ty disorders receiving alprazolam (0.8-2.4 mg/day) ingested grapefruit juic e (600 ml/day) for 7 days. Blood samples were collected before and during g rapefruit juice ingestion and 1 week after its discontinuation together wit h an assessment of clinical status. Grapefruit juice altered neither the st eady-state plasma concentration of alprazolam nor the clinical status in pa tients. The present study shows that grapefruit juice is unlikely to affect pharmacokinetics or pharmacodynamics of alprazolam due to its high bioavai lability.