The effects of grapefruit juice on sertraline metabolism: an in vitro and in vivo study.
Clin Ther 1999 Nov;21(11):1890-9.
Lee AJ, Chan WK, Harralson
AF, Buffum J, Bui BC.
School of Pharmacy and Health Sciences, University of the Pacific, Stockton,
California 95211, USA.
Grapefruit juice is an inhibitor of cytochrome P-450 3A4 (CYP3A4). This study
was designed to assess the in vitro and in vivo effects of grapefruit juice on
sertraline metabolism. The in vitro assay involved analysis of sertraline
metabolism by CYP3A4 using CYP3A4-expressed human beta-lymphoblast microsomes.
The in vivo study involved high-performance liquid chromatographic analysis of
serum trough levels of sertraline and desmethylsertraline in 5 patients who had
been taking their usual dose of sertraline for > or =6 weeks, followed by
concurrent use of sertraline with grapefruit juice for 1 week. The in vitro
assay demonstrated that grapefruit juice inhibited the formation of
desmethylsertraline in a dose-dependent manner. In the in vivo study, mean serum
sertraline levels were determined in 5 patients with a history of depression (4
males and 1 female). The mean age of the patients was 68.6 years, their mean
weight was 69.6 kg, and their mean sertraline dosage was 55 mg/d. The results of
the in vivo study appeared to be consistent with the in vitro findings, in that
mean (+/- SD) serum sertraline trough levels increased significantly from
13.7+/-4.9 microg/L before to 20.2+/-4.4 microg/L (P = 0.047) after
administration of grapefruit juice. Thus the in vitro study demonstrated that
grapefruit juice can inhibit the metabolism of sertraline. A larger study is
warranted to substantiate the clinical significance of the in vivo findings.