Effects of lovastatin on the pharmacokinetics of diltiazem and its main metabolite, desacetyldiltiazem, in rats: possible role of cytochrome P450 3A4 and P-glycoprotein inhibition by lovastatin

Hong, Soon-Pyo; Yang, Joon-Seung; Han, Jung-Yeon; Ha, Sung-Il; Chung, Joong-Wha; Koh, Young‐Youp; Chang, Kyong-Sig; Choi, Dong‐Hyun

doi:10.1111/j.2042-7158.2010.01160.x

Cited by 11 publications

(6 citation statements)

References 39 publications

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“…The transport of Gpz from mucosal to serosal side was increased in the presence of Lov and verapamil (standard P-gp inhibitor). Lov is a P-gp substrate [22] and it also a potent inhibitor of P-gp [23][24][25]. Results were shown in Fig.…”

Section: Discussionmentioning

confidence: 97%

Influence of Lovastatin on Pharmacokinetics and Pharmacodynamics of Glipizide in Healthy and Streptozotocin - Induced Diabetic Rats: Involvement of P-Glycoprotein Inhibition

Kadimpati¹,

Sammeta²,

Pingili

et al. 2016

Asian J Pharm Clin Res

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This study evaluated the effect of lovastatin (Lov) on the pharmacokinetics and pharmacodynamics of glipizide (Gpz) in healthy and streptozotocininduceddiabeticrats.In singledose study(SDS), blood samples werecollectedonthe 1st day, whereas in multiple dose study on the 15 day at0-12 hrs. Lov significantly altered the pharmacokinetic parameters at the dose of 15 mg/kg in SDS and multiple dose study. The C of Gpz wasincreased from 2.97 to 8.38 and 9.87 to 24.58 ng/mL in healthy and diabetic rats, respectively, in multiple dose study. Rat everted sacs were used tostudy the transport of Gpz in the presence of Lov and verapamil (P-glycoprotein [P-gp] inhibitor). The transport of Gpz from mucosal to the serosalsurface was significantly increased from 4.32 to 5.65 and 6.02 µg/mL in the presence of Lov and verapamil, respectively. The interaction between Lovand Gpz is due to P-gp and CYP2C9 inhibition.Keywords: Diabetes, Dyslipidemia, Glipizide, Lovastatin, P-glycoprotein.maxth

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Section: Discussionmentioning

confidence: 97%

Influence of Lovastatin on Pharmacokinetics and Pharmacodynamics of Glipizide in Healthy and Streptozotocin - Induced Diabetic Rats: Involvement of P-Glycoprotein Inhibition

Kadimpati¹,

Sammeta²,

Pingili

et al. 2016

Asian J Pharm Clin Res

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“…Besides, Martirosyan et al found that lovastatin had a synergistic effect with doxorubicin in a dose-dependent manner in ovarian cancer cells treatment through P-gp inhibition increasing doxorubicin systemic exposure [49]. Moreover, co-administration of lovastatin increased AUC 0-∞ and C max of diltiazem and nicardipine by the inhibition of CYP3A4 and P-gp in rats and mice [50,51]. Recently, Sanneboina et al demonstrated that lovastatin increased plasma concentration of glipizide and repaglinide by lovastatin inhibition effect of both P-gp and CYP3A4 in rats and rabbits [52].…”

Section: Discussionmentioning

confidence: 99%

Statins Increase the Bioavailability of Fixed-Dose Combination of Sofosbuvir/Ledipasvir by Inhibition of P-glycoprotein

et al. 2022

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Background Coadministration of statins and direct acting antiviral agents is frequently used. This study explored the effects of both atorvastatin and lovastatin on pharmacokinetics of a fixed-dose combination of sofosbuvir/ledipasvir “FDCSL”. Methods 12 healthy volunteers participated in a randomized, three-phase crossover trial and were administered a single atorvastatin dose 80 mg plus tablet containing 400/90 mg FDCSL, a single lovastatin dose 40 mg plus tablet containing 400/90 mg FDCSL, or tablets containing 400/90 mg FDCSL alone. Liquid chromatography-tandem mass spectrometry was used to analyze plasma samples of sofosbuvir, ledipasvir and sofosbuvir metabolite “GS-331007” and their pharmacokinetic parameters were determined. Results Atorvastatin caused a significant rise in sofosbuvir bioavailability as explained by increasing in AUC0−∞ and Cmax by 34.36% and 11.97%, respectively. In addition, AUC0-∞ and Cmax of GS-331007 were increased by 73.73% and 67.86%, respectively after atorvastatin intake. Similarly, co-administration of lovastatin with FDCSL increased the bioavailability of sofosbuvir, its metabolite (AUC0-∞ increase by 17.2%, 17.38%, respectively, and Cmax increase by 12.03%, 22.24%, respectively). However, neither atorvastatin nor lovastatin showed a change in ledipasvir bioavailability. Hepatic elimination was not affected after statin intake with FDCSL. Compared to lovastatin, atorvastatin showed significant increase in AUC0-∞ and Cmax of both sofosbuvir and its metabolite. Conclusions Both atorvastatin and lovastatin increased AUC of sofosbuvir and its metabolite after concurrent administration with FDCSL. Statins’ P-glycoprotein inhibition is the attributed mechanism of interaction. The increase in sofosbuvir bioavailability was more pronounced after atorvastatin intake. Close monitoring is needed after co-administration of atorvastatin and FDCSL.

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“…Grapefruit juice, if consumed in large amounts, may also significantly increase the inhibitory activity of lovastatin on HMG-CoA reductase 15. Furthermore, there is clear evidence that lovastatin inhibits the membrane transport protein P-glycoprotein, which plays an important role in the detoxification of drugs 1,17,18…”

Section: Pharmacological Effects and Interactions Of Red Yeast Ricementioning

confidence: 99%

“…This efflux transporter, which is predominantly found in excretory tissues, actively transports not only endogenous substances, such as steroids and cytokines, but also potentially toxic xenobiotics out of cells. Thus, the inhibitory effect of monacolin K (lovastatin) on this transporter can also significantly influence the bioavailability and the distribution of drugs 17,18…”

Section: Pharmacological Effects and Interactions Of Red Yeast Ricementioning

confidence: 99%

<p>Mini-review: medication safety of red yeast rice products</p>

Farkouh¹,

Baumgärtel²

2019

IJGM

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High lipid levels in the blood together with high blood pressure and diabetes are among the highest risks for coronary heart disease. In particular, elevated cholesterol levels promote the progression of atherosclerosis. Red yeast rice, also called red fermented rice or red mold rice, is used as a dietary supplement to lower cholesterol levels. It contains varying amounts of natural monacolin K, which is a structural homolog to lovastatin, and shows hypocholesterolemic properties comparable to synthetic statins. Despite being portrayed as a natural alternative, the potential of red yeast rice for side effects and interactions is comparable to statin drugs. Consumers need to be made aware of the varying monacolin K content in red yeast rice products and the insufficient long-term safety data regarding the potential risks of red yeast rice.

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Effects of lovastatin on the pharmacokinetics of diltiazem and its main metabolite, desacetyldiltiazem, in rats: possible role of cytochrome P450 3A4 and P-glycoprotein inhibition by lovastatin

Abstract: It might be considered that lovastatin resulted in reducing the first-pass metabolism in the intestine and/or in the liver via inhibition of CYP3A4 and increasing the absorption of diltiazem in the intestine via inhibition of P-gp by lovastatin.

Cited by 11 publications

References 39 publications

Influence of Lovastatin on Pharmacokinetics and Pharmacodynamics of Glipizide in Healthy and Streptozotocin - Induced Diabetic Rats: Involvement of P-Glycoprotein Inhibition

Influence of Lovastatin on Pharmacokinetics and Pharmacodynamics of Glipizide in Healthy and Streptozotocin - Induced Diabetic Rats: Involvement of P-Glycoprotein Inhibition

Statins Increase the Bioavailability of Fixed-Dose Combination of Sofosbuvir/Ledipasvir by Inhibition of P-glycoprotein

<p>Mini-review: medication safety of red yeast rice products</p>

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