Metabolism and Drug Interactions of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors in Transplant Patients

Christians, Uwe; Jacobsen, Wolfgang; Floren, Leslie Carstensen

doi:10.1016/s0163-7258(98)00016-3

Cited by 208 publications

(145 citation statements)

References 236 publications

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“…Neither of these assumptions may be valid. However, studies do show that calcineurin inhibitors substantially increase the bioavailability of statins, even for pravastatin that is not metabolized by cytochrome P-450 3A4 (14). Furthermore, the doseresponse curve is relatively flat after modest doses of statins (15).…”

Section: Discussionmentioning

confidence: 99%

“…These included a small number of patients with functioning kidney pancreas (14), sequential liver kidney (3) and sequential heart kidney transplants (1).…”

Section: Populationmentioning

confidence: 99%

“…Refractory LDL control was defined as LDL cholesterol >2.6 mmol/L while on statin therapy. The definition did not depend on statin dose or drug, since immunosuppressive medications increase statin exposure and the dose-response curve is relatively flat after moderate statin doses (14,15). Resistant hypertension control was defined as systolic pressure >135 mmHg on 3 or more anti-hypertensive medications (16).…”

Section: Contraindications To Therapy/adverse Eventsmentioning

confidence: 99%

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Cardiovascular Disease Reduction in the Outpatient Kidney Transplant Clinic

Kiberd¹,

Keough-Ryan²,

Panek³

2003

American Journal of Transplantation

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Cardiovascular disease (CVD) is an important cause of death in kidney transplant recipients. Future CVD mortality was estimated by a risk calculator in all patients (n = = 439) with a functioning transplant (>6 months), followed at our center. In addition to CURRENT mortality rates, an OPTIMAL rate (adding anti-hypertensive and lipid-lowering therapy in uncontrolled patients) and an HISTORIC rate (higher systolic blood pressures and the absence of statin use in our population 5 years ago) were also calculated. Overall, the predicted CUR-RENT CVD mortality rates are 0.82 (95% CI 0.81-0.83) of HISTORIC rates. Predicted OPTIMAL CVD mortality rates are 0.90 (95% CI 0.87-0.92) of CURRENT rates. To achieve OPTIMAL rates, a 27% increase in blood pressure and lipid-lowering drug use is required. There were few contraindications to these medications, implying that physician prescribing was the major barrier to minimizing risk. Despite OPTIMAL rates, the transplant population's relative risk is 2.3 (median, 95% CI 2.1-2.5) times higher than that in the general population. Therefore, targeted therapy to reduce CVD risk can have substantial benefit, but CVD mortality may continue to exceed that in the general population.

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Section: Discussionmentioning

confidence: 99%

“…These included a small number of patients with functioning kidney pancreas (14), sequential liver kidney (3) and sequential heart kidney transplants (1).…”

Section: Populationmentioning

confidence: 99%

Section: Contraindications To Therapy/adverse Eventsmentioning

confidence: 99%

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Cardiovascular Disease Reduction in the Outpatient Kidney Transplant Clinic

Kiberd¹,

Keough-Ryan²,

Panek³

2003

American Journal of Transplantation

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“…Fluvastatin, an HMG-CoA reductase inhibitor, which is the first wholly synthetic statin on the market, has been widely used as a classic lipid-regulating drug to treat hypercholesterolemia [7] . The advantages of fluvastatin, compared to other statins, are as follows: fluvastatin is well tolerated [8,9] , substantial benefits of fluvastatin have been confirmed in clinical trials [10] , and fluvastatin is more cost effective for long-term treatment [11] . Beyond its regulation of blood lipids, the antiatherogenic, antithrombotic and antioxidative actions of fluvastatin have been used to prevent cardiovascular disease [12] .…”

Section: Introductionmentioning

confidence: 99%

Influence of fluvastatin on cardiac function and baroreflex sensitivity in diabetic rats

Xie

Sun

et al. 2011

Acta Pharmacol Sin

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Aim: To investigate whether fluvastatin is able to ameliorate the impaired cardiac function or baroreflex sensitivity (BRS) in rats with type 1 diabetes. Methods: Type 1 diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ) and then administered fluvastatin (1.5, 3.0, and 6.0 mg·kg -1 ·d -1 ) for 30 d. Food and drink intake was recorded every day. Fasting blood glucose (FBG) level, blood lipid level, cardiac function and BRS were measured in diabetic rats after fluvastatin treatment for 30 d. Results: The polydipsia, polyphagia and abnormal biochemical indexes of blood were significantly ameliorated by the the 3.0-and 6.0-mg doses of fluvastatin in STZ-induced diabetic rats. FBG was decreased in diabetic rats after fluvastatin treatment for 30 d. The left ventricular systolic pressure (LVSP) and the maximum rate of change of left ventricular pressure in the isovolumic contraction and relaxation period (±dp/dt max ) were elevated, and left ventricular diastolic pressure (LVEDP) was decreased by fluvastatin. The attenuated heart rate responses to arterial blood pressure (ABP) increase induced by phenylephrine (PE) and ABP decrease induced by sodium nitroprusside (SNP) were reversed by the 3.0-mg dose of fluvastatin. Conclusion: Fluvastatin regulates blood lipid levels and decreases the FBG level in diabetic rats. These responses can protect the diabetic heart from complications by improving cardiac function and BRS.

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“…Numerous statins are substrates of CYP450, organic anion-transporting polypeptide (OATP)-1B1/3, and other transporters and metabolizing enzymes [3][4][5].Both simvastatin and lovastatin are prodrugs that require activation to simvastatin acid and lovastatin acid, respectively. Simvastatin and lovastatin are the principal CYP3A4 substrates, followed by atorvastatin [5][6][7][8], while fluvastatin and rosuvastatin is a CYP2C9 substrate [9,10].…”

Section: Statin Metabolismmentioning

confidence: 99%

An updated review of interactions of statins with antibacterial and antifungal agents

Eljaaly¹,

Alshehri²

2017

J Transl Sci

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Numerous antimicrobial agents interact with statins. It is important to prevent these drug interactions and resulting statin toxicity and/or reduced efficacy. We review and highlight major drug-drug interactions between statins and antibacterial and antifungal agents; interactions with antiviral agents were not considered. Daptomycin interacts with statins via additive skeletal muscle toxicity. One possibility is to discontinue statins during daptomycin therapy, though no retrospective studies to date have shown a statistically significant elevation of adverse outcome risk. Multiple doses of rifampin induce cytochrome P450 (CYP), particularly 3A4 and 2C9, resulting in reduced systemic exposures to all statins, except rosuvastatin, for which the response was variable. Macrolide antibiotics are inhibitors of CYP3A4 and organic anion-transporting polypeptide-1B1. Azithromycin has the fewest drug interactions, while clarithromycin and erythromycin increase systemic exposure to all statins except rosuvastatin and fluvastatin. Azole antifungals are CYP450 inhibitors. Itraconazole and posaconazole are strong CYP3A4 inhibitors and mainly affect simvastatin, lovastatin, and atorvastatin, while fluconazole is an inhibitor of CYP2C9 and potentially CYP2C19 and mainly affects fluvastatin; however, risk cannot be ruled out with rosuvastatin.

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Metabolism and Drug Interactions of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors in Transplant Patients

Cited by 208 publications

References 236 publications

Cardiovascular Disease Reduction in the Outpatient Kidney Transplant Clinic

Cardiovascular Disease Reduction in the Outpatient Kidney Transplant Clinic

Influence of fluvastatin on cardiac function and baroreflex sensitivity in diabetic rats

An updated review of interactions of statins with antibacterial and antifungal agents

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