More potent lipid-lowering effect by rosuvastatin compared with fluvastatin in everolimus-treated renal transplant recipients.

Abstract

BACKGROUND:

Dyslipidemia is a risk factor for premature cardiovascular morbidity and mortality in renal transplant recipients (RTRs). Pharmacotherapy with mTOR inhibitors aggravates dyslipidemia, thus necessitating lipid-lowering therapy with fluvastatin, pravastatin, or atorvastatin. These agents may not sufficiently lower lipid levels, and therefore, a more potent agent like rosuvastatin maybe needed.

METHODS:

We have aimed to assess the lipid-lowering effect of rosuvastatin as compared with fluvastatin in RTR receiving everolimus. Safety was assessed as the pharmacokinetic (PK) interaction potential of a rosuvastatin/everolimus combination in RTR. A 12-hour everolimus PK investigation was performed in 12 stable RTR receiving everolimus and fluvastatin (80 mg/d). Patients were then switched to rosuvastatin (20 mg/d), and a follow-up 12/24-hour PK investigation of everolimus/rosuvastatin was performed after 1 month. All other drugs were kept unchanged.

RESULTS:

In RTR already receiving fluvastatin, switching to rosuvastatin further decreased LDL cholesterol and total cholesterol by 30.2±12.2% (P<0.01) and 18.2±9.6% (P<0.01), respectively. Everolimus AUC0-12 was not affected by concomitant rosuvastatin treatment, 80.3±21.3 μg*h/L before and 78.5±21.9 μg*h/L after, respectively (P=0.61). Mean rosuvastatin AUC0-24 was 157±61.7 ng*h/mL, approximately threefold higher than reported in the literature for nontransplants. There were no adverse events, and none of the patients had or developed proteinuria.

CONCLUSION:

Rosuvastatin showed a superior lipid-lowering effect compared to fluvastatin in stable RTR receiving everolimus. The combination of everolimus/rosuvastatin seems to be as safe as the everolimus/fluvastatin combination.

• Authors: Ida Robertsen, Anders Asberg, Tone Granseth, Nils Tore Vethe, Fatemeh Akhlaghi, Mwlod Ghareeb, Espen Molden, Morten Reier-Nilsen, Hallvard Holdaas, Karsten Midtvedt
• Journal: Transplantation (Transplantation) Vol. 97 Issue 12 Pg. 1266-71 (Jun 27 2014) ISSN: 1534-6080 [Electronic] United States
• PMID: 24521776 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Biomarkers
• Fatty Acids, Monounsaturated
• Fluorobenzenes
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Immunosuppressive Agents
• Indoles
• Lipids
• Pyrimidines
• Sulfonamides
• Fluvastatin
• Rosuvastatin Calcium
• Everolimus
• CYP3A5 protein, human
• Cytochrome P-450 CYP3A
• Sirolimus

Topics

• Aged
• Biomarkers (blood)
• Cytochrome P-450 CYP3A (genetics, metabolism)
• Drug Interactions
• Drug Substitution
• Dyslipidemias (blood, drug therapy, etiology)
• Everolimus
• Fatty Acids, Monounsaturated (adverse effects, pharmacokinetics, therapeutic use)
• Female
• Fluorobenzenes (adverse effects, pharmacokinetics, therapeutic use)
• Fluvastatin
• Genotype
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (adverse effects, pharmacokinetics, therapeutic use)
• Immunosuppressive Agents (adverse effects, pharmacokinetics, therapeutic use)
• Indoles (adverse effects, pharmacokinetics, therapeutic use)
• Kidney Transplantation (adverse effects)
• Lipids (blood)
• Male
• Middle Aged
• Norway
• Phenotype
• Prospective Studies
• Pyrimidines (adverse effects, pharmacokinetics, therapeutic use)
• Rosuvastatin Calcium
• Sirolimus (adverse effects, analogs & derivatives, pharmacokinetics, therapeutic use)
• Sulfonamides (adverse effects, pharmacokinetics, therapeutic use)
• Treatment Outcome