Evaluation of the pharmacokinetic interaction between fluvastatin XL and cyclosporine in renal transplant recipients

Holdaas, H.; Hagen, Edward H.; Åsberg, Anders; Lund, K; Hartman, Anders; Vaidyanathan, Seema; Prasad, Pallavi; Yl, He; Cm, Yeh; Bigler, Hilde; Rouilly, Marisel; Denouël, J.

doi:10.5414/cpp44163

Cited by 24 publications

(11 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Especially, the coadministration of cyclosporin A increased C max and the AUC of pravastatin 7–8 times and 12 times higher, respectively, in humans (41). In contrast, those of fluvastatin were only 2–3 times higher with cyclosporin A than with mono‐administration (42). This may explain the reason why the reported cases of rhabdomyolysis is greater for pravastatin than fluvastatin.…”

Section: Discussionmentioning

confidence: 99%

Rab‐small GTPases are involved in fluvastatin and pravastatin‐induced vacuolation in rat skeletal myofibers

Sakamoto¹,

Honda²,

Yokoya³

et al. 2007

FASEB j.

View full text Add to dashboard Cite

Three-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors, known as statins, induce skeletal muscle injury including myalgia, myositis, and rhabdomyolysis. The mechanism of this myotoxicity remains unknown. This study examined the effect of statins on single skeletal myofibers enzymatically isolated from the rat flexor digitorum brevis muscles. Fluvastatin and pravastatin induced the formation of numerous vacuoles in the myofibers after 72 h of treatment. This effect progressed in a time- and concentration-dependent manner and, consequently, cell death occurred after 120 h. Electron micrographs revealed craters along the sarcolemma and swelling of the sarcoplasmic reticula and mitochondria, in addition to intracellular vacuoles. When caffeine was added after 72 h of fluvastatin treatment, contractile shortening of statin-treated myofibers was significantly attenuated and blebs formed on the surface of the myofibers. The coapplication of geranylgeranylpyrophosphate (GGPP) with fluvastatin prevented the morphological changes, while that of farnesylpyrophosphate (FPP) was ineffective. Furthermore, perillyl alcohol, an inhibitor of Rab geranylgeranyl transferase and geranylgeranyl transferase-I (GGTase-I), mimicked the effect of statins, while a specific GGTase-I inhibitor (GGTI-298) or a farnesyl transferase inhibitor (FTI-277) failed to do so. These results suggest that the inactivation of Rab GTPase, which involved in intracellular membrane transport, is a crucial factor in statin-induced-morphological abnormality in skeletal muscle fibers.

show abstract

Section: Discussionmentioning

confidence: 99%

Rab‐small GTPases are involved in fluvastatin and pravastatin‐induced vacuolation in rat skeletal myofibers

Sakamoto¹,

Honda²,

Yokoya³

et al. 2007

FASEB j.

View full text Add to dashboard Cite

show abstract

“…Consequently, the statin therapy in cyclosporine A-treated transplant recipients should be initiated at the lower end of the dosage range. In contrast, fluvastatin has a low interaction with cyclosporine A because it is mainly metabolized by CYP2C9 (Holdaas et al, 2006).…”

Section: Statins and Cancer: Pros And Consmentioning

confidence: 99%

Pharmacological Actions of Statins: A Critical Appraisal in the Management of Cancer

Gazzerro

Proto²,

Gangemi³

et al. 2011

Pharmacol Rev

398

370

View full text Add to dashboard Cite

“…Pravastatin and fluvastatin are the preferred lipid-lowering therapies in solid organ transplant recipients, because of the relatively low risk of interaction with CsA (Holdaas et al, 2006;Skalicka et al, 2009). However, in patients with severe hyperlipidemia the efficacy of these two statins may become inadequate.…”

Section: Introductionmentioning

confidence: 99%

Cyclosporine A, but Not Tacrolimus, Shows Relevant Inhibition of Organic Anion-Transporting Protein 1B1-Mediated Transport of Atorvastatin

Amundsen¹,

Christensen²,

Zabihyan³

et al. 2010

Drug Metab Dispos

127

107

View full text Add to dashboard Cite

ABSTRACT:The aim of this study was to investigate the potential of calcineurin inhibitors [cyclosporine A (CsA) and tacrolimus (Tac)] to inhibit cellular uptake of atorvastatin mediated by the liver-specific organic anion-transporting polypeptide 1B1 ( The IVIVE showed that clinically obtainable concentrations of CsA, but not Tac, inhibit OATP1B1 transport of atorvastatin. CsA inhibition ranged from 28 to 77% within a dosing interval, whereas it was less than 1% for Tac, considering free concentrations and assuming competitive inhibition. This does not fully explain the clinically observed interaction with CsA, suggesting that a more complex inhibitory mechanism may be present. This is also supported by the decreased IC 50 value of CsA after preincubation. This study provides evidence that OATP1B1 inhibition is a relevant mechanism for the interaction observed between CsA and atorvastatin.

show abstract

Evaluation of the pharmacokinetic interaction between fluvastatin XL and cyclosporine in renal transplant recipients

Cited by 24 publications

References 0 publications

Rab‐small GTPases are involved in fluvastatin and pravastatin‐induced vacuolation in rat skeletal myofibers

Rab‐small GTPases are involved in fluvastatin and pravastatin‐induced vacuolation in rat skeletal myofibers

Pharmacological Actions of Statins: A Critical Appraisal in the Management of Cancer

Cyclosporine A, but Not Tacrolimus, Shows Relevant Inhibition of Organic Anion-Transporting Protein 1B1-Mediated Transport of Atorvastatin

Contact Info

Product

Resources

About