Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine

摘要: Aims To determine whether repeated once daily administration of grapefruit juice altered the pharmacokinetics or pharmacodynamics calcium antagonist amlodipine. Methods The effects on and oral intravenous amlodipine were assessed in 20 healthy men a placebo-controlled, open, randomized, four-way crossover study using single doses 10 mg. For 9 days beginning with day amlodipine, (or water control) was given daily, blood samples, pressure heart rate measures obtained. Plasma concentrations its enantiomers determined separate assays by GC-ECD. Results Oral had high systemic availability (grapefruit juice: 88%; water: 81%). Pharmacokinetic parameters racemic (AUC, Cmax, tmax, kel) not markedly changed coadministration. Total plasma clearance volume distribution, calculated after essentially unchanged (CL 6.65 ml min x1 kg , vs 6.93 water; Vdss 22.7 l 21.0 water). Grapefruit coadministration did greatly alter stereoselectivity kinetics. sum S(‐) R(+) enantiomer correlated well total concentration (r 2 =0.957; P=0.0001). Coadministration either route significantly changes control. Conclusions has no appreciable effect pharmacokinetics, including stereoselective Bioavailability enhancement juice, noted other dihydropyridine antagonists, does occur Once usual is unlikely to profile response clinical practice.