Effect of Grapefruit juice on the pharmacokinetics of losartan in healthy volunteers

Losartan (LOS) an angiotensin receptor blocker is metabolized to E-3174 through cytochrome P-450 (CYP) isoenzymes CYP3A4 and CYP2C9, Grapefruit juice (GJ) inhibits CYP3A4. Thus the effect of GJ on the pharmacokinetics of a single dose of LOS in healthy volunteers was investigated. Methods: Nine healthy volunteers aged 29-50 years were given on day one 200 ml of water 1 hour before and together with morning LOS. Following a week of washout LOS was given with 200 ml of GJ in the same order, serial blood samples were collected. Plasma concentrations of LOS and E-3174 were determined by HPLC. Results: Ingestion of GJ increases the AUC of LOS as compared to water from 34787±11040 to 39731±11091 ng/ml/min. However AUC of E-3174 decreases after GJ from 164675±67422 to 133374±43728. Conclusions: Coadministration of LOS and GJ produces a statistically significant increase in AUC of LOS and decrease in AUC of E-3174 in healthy volunteers. Concomitant ingestion of LOS and GJ may reduce LOS' clinical effect.