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 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.