The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study

Grapefruit juice is an inhibitor of cytochrome P-450 3A4 (CYP3A4). This stu dy was designed to assess the in vitro and in vivo effects of grapefruit ju ice on sertraline metabolism. The in vitro assay involved analysis of sertr aline metabolism by CYP3A4 using CYP3A4-expressed human beta-lymphoblast mi crosomes; The in vivo study involved. high-performance liquid chromatograph ic analysis of serum trough levels of sertraline and des methylsertraline i n 5 patients who had been taking their usual dose of sertraline for greater than or equal to 6 weeks, followed by concurrent use of sertraline with gr apefruit juice for 1 week. The in vitro assay demonstrated that grapefruit juice inhibited the formation of desmethylsertraline in a dose-dependent ma nner. 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 a ge 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 appea red to be consistent with the in vitro findings, in that mean (+/- SD) seru m sertraline trough levels increased significantly from 13.7 +/- 4.9 mu g/L before to 20.2 +/- 4.4 mu g/L (P = 0.047) after administration of grapefru it juice. Thus the in vitro study demonstrated that grapefruit juice can in hibit the metabolism of setraline. A larger study is warranted to substanti ate the clinical significance of the in vivo findings.