Interaction between Red Yeast Rice and CYP450 Enzymes/P-Glycoprotein and Its Implication for the Clinical Pharmacokinetics of Lovastatin

Abstract

Red yeast rice (RYR) can reduce cholesterol through its active component, lovastatin. This study was to investigate the pharmacokinetic properties of lovastatin in RYR products and potential RYR-drug interactions. Extracts of three registered RYR products (LipoCol Forte, Cholestin, and Xuezhikang) were more effective than pure lovastatin in inhibiting the activities of cytochrome P450 enzymes and P-glycoprotein. Among CYP450 enzymes, RYR showed the highest inhibition on CYP1A2 and CYP2C19, with comparable inhibitory potencies to the corresponding typical inhibitors. In healthy volunteers taking the RYR product LipoCol Forte, the pharmacokinetic properties of lovastatin and lovastatin acid were linear in the dose range of 1 to 4 capsules taken as a single dose and no significant accumulation was observed after multiple dosing. Concomitant use of one LipoCol Forte capsule with nifedipine did not change the pharmacokinetics of nifedipine. Yet, concomitant use of gemfibrozil with LipoCol Forte resulted in a significant increase in the plasma concentration of lovastatin acid. These findings suggest that the use of RYR products may not have effects on the pharmacokinetics of concomitant comedications despite their effects to inhibit the activities of CYP450 enzymes and P-gp, whereas gemfibrozil affects the pharmacokinetics of lovastatin acid when used concomitantly with RYR products.

Comparison of the Reduction of LDL-C or nonHDL-C induced by Red Yeast Rice Extract, Xuezhikang, between Fasting and Postprandial States in Patients with Coronary Artery Disease

“…There is 24 mg of natural statins in each Xuezhikang capsule. Additionally, it comprises unsaturated fatty acids and sterols that could help to lower blood lipids [23]. Compared with 10 mg lovastatin, 1200 mg Xuezhikang has stronger effects on lowering cholesterol and TG levels [23,24].…”

“…Additionally, it comprises unsaturated fatty acids and sterols that could help to lower blood lipids [23]. Compared with 10 mg lovastatin, 1200 mg Xuezhikang has stronger effects on lowering cholesterol and TG levels [23,24]. Just because of the ability to improve blood lipids at both fasting and postprandial states, Xuezhikang was found to effectively reduced the risk of myocardial infarction and death in Chinese patients with CAD [25].…”

A Review of the Toxicity of HIV Medications II: Interactions with Drugs and Complementary and Alternative Medicine Products

“…It is thought to inhibit CYP1A2 and 2C19; however, no ARV interactions have been reported to date [118]. Similarly, the administration of milk thistle (Silymarin marianum), taken to help treat liver disease and prevent hepatotoxicity via antioxidant properties, has not been shown to significantly affect darunavir-ritonavir concentrations [119].…”

Effect of a Combination of Berberine and Monacolin on CYP Enzymes: An Oral Cocktail Interaction Study in Healthy Volunteers

“…Berberine is metabolised predominantly by CYP2D6, but also by CYP3A4 and CYP1A2 [10,11] and was found to be an inhibitor of CYP2D6, CYP3A4 and CYP2C9 [12]. Monacolin is metabolized by CYP3A4 [13,14] and was found to be an inhibitor of CYP2C9, CYP2C19 and CYP3A4 [15]. CYP inhibition is very often responsible for clinically relevant drug interaction and there is increasing evidence that herb-drug interactions may be attributable to the inhibition of hepatic and intestinal drug-metabolizing enzymes by herbs [2].…”