Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin

Abstract

Grapefruit juice significantly increased serum concentrations of atorvastatin acid, atorvastatin lactone, and active and total HMG-CoA reductase inhibitors, probably by decreasing CYP3A4-mediated first-pass metabolism of atorvastatin in the small intestine. On the other hand, grapefruit juice had no effect on the pharmacokinetics of pravastatin. Concomitant use of atorvastatin and at least large amounts of grapefruit juice should be avoided, or the dose of atorvastatin should be reduced accordingly.

Effects of Acid and Lactone Forms of Eight HMG-CoA Reductase Inhibitors on CYP-Mediated Metabolism and MDR1-Mediated Transport

“…Herein, we elucidated that the lactone forms of atorvastatin and rosuvastatin inhibit CYP2C9 or CYP3A4/5 activities (Table I). Taken together, the recently reported drug interaction of atorvastatin or rosuvastatin can be explained by the actions of the lactone form, which can be transformed in the body, and not by that of the acid form, which is that in the medicine (26,30).…”

Differential Effect of Grapefruit Juice on Intestinal Absorption of Statins Due to Inhibition of Organic Anion Transporting Polypeptide and/or P-glycoprotein

“…1a). 38,39 As shown in Figure 4a, naringin inhibited OATP1A2-mediated, but not OATP2B1-mediated, transport of pravastatin. On the basis of the increasing evidence that intestinal absorption of various drugs is mediated by OATP2B1, OATP2B1 may be a major determinant of the intestinal absorption of pravastatin in humans, as compared with OATP1A2.…”

Bioavailability and Bioequivalence

“…The observed increase in felodipine bioavailability was presumed to result from inhibition of intestinal CYP3A4, as a lack of effect on hepatic CYP3A4 activity by grapefruit juice was determined by the IV erythromycin breath test. Grapefruit juice interaction studies have indicated that intestinal metabolism may also contribute to the first-pass elimination of saquinavir [102] and atorvastatin [103]. A representative group of drugs that undergo presystemic elimination and the proportion attributed to intestinal first-pass metabolism is shown in Table 10.5.…”