The effect of orange juice on the pharmacokinetics of the 3-hydroxy-3-methylglutaryl COA (HMG-COA) reductase inhibitor pravastatin

Objectives It has been reported that lipophilic drug bioavailability was changed by grapefruit juice intake with its inhibitory effect on CYP3A4, or on efflux transporter P-glycoprotein. On the other hand, pravastatin(PRV) as hydrophilic HMG-CoA reductase inhibitor may be absorbed via intestinal OATP (organic anion transporter protein) and MRP2 (multidrug resistance associsted protein 2), hydrophilic membrance transporters. Dresser et al suggested orange juice (OJ) as the inhibitor of OATPs by showing the reduction of bioavailability of antihistaminic drug fexofenadin in humans. Thus, we studied the effect of OJ on the pharmacokinetics (PK) of PRV when co-administrated with OJ.Results and Methods Male Wistar rats were used. Rat was gived 100mg/kg (P.O) single dose PRV with water (control) or OJ, and the PK of PRV was investigated. Serum concentrations of PRV were quantified by HPLC in this study. OJ increased significantly peak serum concentration and AUC of PRV (153%,141%),respectively, whereas the elimination half-life was not changed significantly.Discussion Our data suggested that OJ increased oral PRV bioavailability, while not on clearance. This may be explained by altered intestinal pH which can change the OATP function, or by the direct effect on the transporters with ingredients of OJ.Clinical Pharmacology & Therapeutics (2004) 75, P77–P77; doi: 10.1016/j.clpt.2003.11.293