Effects of lovastatin on the pharmacokinetics of nicardipine in rats

Chung, Joong-W.; Yang, Sihyung; Choi, Jun-S.

doi:10.1002/bdd.721

Cited by 7 publications

(5 citation statements)

References 21 publications

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“…Nicardipine has been reported to be a substrate of CYP3A4 and P-glycoprotein (P-gp) in humans,21 and lovastatin is a dual inhibitor of both CYP3A4 and P-gp 11. Therefore, lovastatin could affect the pharmacokinetics of nicardipine when they are used concomitantly for the prevention or therapy of cardiovascular diseases.…”

Section: Resultsmentioning

confidence: 99%

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Pharmacokinetic drug–drug interactions between 1,4-dihydropyridine calcium channel blockers and statins: factors determining interaction strength and relevant clinical risk management

Zhou¹,

Yu²,

Zeng³

et al. 2013

TCRM

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BackgroundCoadministration of 1,4-dihydropyridine calcium channel blockers (DHP-CCBs) with statins (or 3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase inhibitors) is common for patients with hypercholesterolemia and hypertension. To reduce the risk of myopathy, in 2011, the US Food and Drug Administration (FDA) Drug Safety Communication set a new dose limitation for simvastatin, for patients taking simvastatin concomitantly with amlodipine. However, there is no such dose limitation for atorvastatin for patients receiving amlodipine. The combination pill formulation of amlodipine/atorvastatin is available on the market. There been no systematic review of the pharmacokinetic drug–drug interaction (DDI) profile of DHP-CCBs with statins, the underlying mechanisms for DDIs of different degree, or the corresponding management of clinical risk.MethodsThe relevant literature was identified by performing a PubMed search, covering the period from January 1987 to September 2013. Studies in the field of drug metabolism and pharmacokinetics that described DDIs between DHP-CCB and statin or that directly compared the degree of DDIs associated with cytochrome P450 (CYP)3A4-metabolized statins or DHP-CCBs were included. The full text of each article was critically reviewed, and data interpretation was performed.ResultsThere were three circumstances related to pharmacokinetic DDIs in the combined use of DHP-CCB and statin: 1) statin is comedicated as the precipitant drug (pravastatin–nimodipine and lovastatin–nicardipine); 2) statin is comedicated as the object drug (isradipine–lovastatin, lacidipine–simvastatin, amlodipine–simvastatin, benidipine-simvastatin, azelnidipine– simvastatin, lercanidipine–simvastatin, and amlodipine–atorvastatin); and 3) mutual interactions (lercanidipine–fluvastatin). Simvastatin has an extensive first-pass effect in the intestinal wall, whereas atorvastatin has a smaller intestinal first-pass effect. The interaction with simvastatin seems mainly driven by CYP3A4 inhibition at the intestinal level, whereas the interaction with atorvastatin is more due to hepatic CYP3A4 inhibition. The interaction of CYP3A4 inhibitor with simvastatin has been more pronounced compared with atorvastatin. From the current data, atorvastatin seems to be a safer CYP3A4-statin for comedication with DHP-CCB. There is no convincing evidence that amlodipine is an unusual DHP-CCB, either as a precipitant drug or as an object drug, from the perspective of CYP3A4-mediated drug metabolism. Amlodipine may have interactions with CYP3A5 in addition to CYP3A4, which may explain its particular characteristics in comparison with other DHP-CCBs. The degree of DDIs between the DHP-CCB and statin and the clinical outcome depends on many factors, such as the kind of statin, physicochemical proprieties of the DHP-CCB, the dose of either the precipitant drug or the object drug, the sex of the patient (eg, isradipine–lovastatin), route of drug administration (eg, oral versus intravenous nicardipine–lovastatin), the administration sch...

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Section: Resultsmentioning

confidence: 99%

“…Because the DHP-CCBs are vasodilators, it is possible that they could increase hepatic blood flow and thereby increase lovastatin clearance 12. It is very necessary to investigate the effect of nicardipine on lovastatin pharmacokinetics, which was not addressed in the study by Chung et al11…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetic drug–drug interactions between 1,4-dihydropyridine calcium channel blockers and statins: factors determining interaction strength and relevant clinical risk management

Zhou¹,

Yu²,

Zeng³

et al. 2013

TCRM

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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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“…nicardipine in rats. [29] The pharmacokinetics of i.v. nimodipine was not affected by the concurrent use of pravastatin in contrast to those of oral administration of nimodipine.…”

Section: Discussionmentioning

confidence: 99%

Effects of pravastatin on the pharmacokinetic parameters of nimodipine after oral and intravenous administration in rats: Possible role of CYP3A4 inhibition by pravastatin

Lee

Choi

2012

Indian J Pharmacol

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Objective:The aim of this study was to investigate the effects of pravastatin on the pharmacokinetics of nimodipine in rats.Materials and Methods:The effect of pravastatin on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activity was evaluated. Nimodipine was administered to rats intravenously (3 mg/kg) and orally (12 mg/kg) with pravastatin (0.3 and 1 mg/kg).Results:Pravastatin inhibited CYP3A4 enzyme activity in a concentration-dependent manner with a 50% inhibition concentration (IC50) of 14 µM. Compared with the oral control group, the area under the plasma concentration-time curve (AUC0-∞) of nimodipine was increased significantly. Consequently, the absolute bioavailability (AB) of nimodipine with pravastatin (1 mg/kg) was 31.1%, which was significantly enhanced compared with the oral control group. Moreover, the relative bioavailability (RB) of nimodipine was 1.12- to 1.31-fold greater than that of the control group.Conclusions:The enhanced oral bioavailability of nimodipine might be mainly due to inhibition of the CYP3A-mediated metabolism of nimodipine in the small intestine and/or in the liver and due to reduction of the total body clearance rather than both to inhibition of the P-gp efflux transporter in the small intestine and reduction of renal elimination of nimodipine by pravastatin. The increase in the oral bioavailability of nimodipine with pravastatin should be taken into consideration of potential drug interactions between nimodipine and pravastatin.

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Effects of lovastatin on the pharmacokinetics of nicardipine in rats

Cited by 7 publications

References 21 publications

Pharmacokinetic drug–drug interactions between 1,4-dihydropyridine calcium channel blockers and statins: factors determining interaction strength and relevant clinical risk management

Pharmacokinetic drug–drug interactions between 1,4-dihydropyridine calcium channel blockers and statins: factors determining interaction strength and relevant clinical risk management

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

Effects of pravastatin on the pharmacokinetic parameters of nimodipine after oral and intravenous administration in rats: Possible role of CYP3A4 inhibition by pravastatin

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Effects of lovastatin on the pharmacokinetics of nicardipine in rats

Cited by 7 publications

References 21 publications

Pharmacokinetic drug&ndash;drug interactions between 1,4-dihydropyridine calcium channel blockers and statins: factors determining interaction strength and relevant clinical risk management

Pharmacokinetic drug&ndash;drug interactions between 1,4-dihydropyridine calcium channel blockers and statins: factors determining interaction strength and relevant clinical risk management

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

Effects of pravastatin on the pharmacokinetic parameters of nimodipine after oral and intravenous administration in rats: Possible role of CYP3A4 inhibition by pravastatin

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Pharmacokinetic drug–drug interactions between 1,4-dihydropyridine calcium channel blockers and statins: factors determining interaction strength and relevant clinical risk management

Pharmacokinetic drug–drug interactions between 1,4-dihydropyridine calcium channel blockers and statins: factors determining interaction strength and relevant clinical risk management