Effects of grapefruit juice on the pharmacokinetics of acebutolol.
OBJECTIVE
We aimed to investigate effects of grapefruit juice on acebutolol pharmacokinetics.


METHODS
In a randomized cross-over study, 10 healthy subjects ingested 200 mL grapefruit juice or water three times daily for 3 days and twice on day 4. On day 3, each subject ingested 400 mg acebutolol with grapefruit juice or water. The concentrations of acebutolol and its metabolite diacetolol were measured in plasma and urine up to 33 h.


RESULTS
Grapefruit juice decreased the peak plasma concentration (Cmax) of acebutolol by 19% from 872 +/- 207 ng mL(-1) to 706 +/- 140 ng mL(-1) (95% CI on the difference -306, -26.4; P < 0.05), and the area under the concentration time curve (AUC(0-33 h)) by 7%, from 4498 +/- 939 ng mL(-1) h to 4182 +/- 915 ng mL(-1) h (95% CI -609, -23.0; P < 0.05). The half-life (t1/2) of acebutolol prolonged from 4.0 to 5.1 h (P < 0.05). The time to peak concentration and the amount of acebutolol excreted into urine (Ae) were unchanged. The Cmax, AUC(0-33 h), and Ae of diacetolol were decreased by 24% (P < 0.05), 18% (P < 0.05), and 20% (P < 0.01), respectively, by grapefruit juice.


CONCLUSIONS
Grapefruit juice caused a small decrease in the plasma concentrations of acebutolol and diacetolol by interfering with gastrointestinal absorption. The interaction between the grapefruit juice and acebutolol is unlikely to be of clinical significance in most of the patients.
Lilja
Jari J
JJ
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. jari.lilja@hus.fi
Raaska
Kari
K
Neuvonen
Pertti J
PJ
D000070:Acebutolol / Q000031:analogs & derivatives / Q000097:blood* / Q000652:urine; D000319:Adrenergic beta-Antagonists / Q000097:blood* / Q000652:urine; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000652:urine; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001628:Beverages; D032083:Citrus paradisi; D018592:Cross-Over Studies; D005260:Female; D018565:Food-Drug Interactions; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; C025527:diacetolol; D000070:Acebutolol