Rosuvastatin Cyclosporine

D. W. (2004) Rosuvastatin pharmacokinetics in heart transplant recipients administered an antirejection regimen including cyclosporine. Clinical Pharmacology and Therapeutics, 76, 167-177. 

Dosage in patients taking cyclosporine - In patients taking cyclosporine, limit therapy to rosuvastatin 5 mg once daily. 

Simonson, S.G., Raza, A., Martin, P.D., Mitchell, P.D., Jarcho, J.A., Brown, C.D.A., Windass, A.S. and Schneck, D.W. (2004) Rosuvastatin pharmacokinetics in heart transplant recipients administered an antirejection regimen including cyclosporine. Clinical Pharmacology and Therapeutics (St. Louis), 76, 167-177. 

The catabolism of lovastatin, simvastatin, and atorvastatin proceeds chiefly through CYP3A4, whereas that of fluvastatin and rosuvastatin is mediated by CYP2C9. Pravastatin is catabolized through other pathways, including sulfation. The 3A4-dependent reductase inhibitors tend to accumulate in plasma in the presence of drugs that inhibit or compete for the 3A4 cytochrome. These include the macrolide antibiotics, cyclosporine, ketoconazole and its congeners, HIVprotease inhibitors, tacrolimus, nefazodone, fibrates, and others (see Chapter 4). Concomitant use of reductase inhibitors with amiodarone or verapamil also causes an increased risk of myopathy. 

Clinically important, potentially hazardous interactions with atorvastatin, bexarotene, cyclosporine, dicumarol, ezetimibe, fluvastatin, interferon alfa, lovastatin, nicotinic acid, pioglitazone, pravastatin, repaglinide, rosuvastatin, roxithromycin, simvastatin, statins, warfarin... 

Cyclosporine 7 11 making rosuvastatin dosing decisions for patients of Japanese and Chinese ancestry Patients taking cyclosporine... 

OATPIBI (SLCO) Cyclosporine A Rosuvastatin 7-fold increase in AUC Inhibition of hepatic sinusoidal OATPIBI and also inhibition of CYP2C BCRP ... 

Cyclosporine increases the systemic exposure of all statins (lovastatin, simvastatin, pravastatin, cerivastatin, and rosuvastatin), due to drug-drug interaction (via either CYPs or transporters like P-gp and OATP) in the liver. Rosuvastatin has been shown to be a substrate for the human liver transporter OATP2 and BCRP, but not P-gp. It s metabolic clearance is low and mainly mediated by CYP2C9. CsA treatment in transplant recipients increased AUCq 2h and Cmax of rosuvastatin (10 mg) by 7.1 and 10.6-fold, respectively, compared with control values, due to CsA inhibition of OATP2-mediated rosuvastatin hepatic uptake (Simonson et al., 2004). 

BCRP (ABCG2) The breast cancer resistance protein (BCRP) transporter is also known as mitoxantrone resistance (MXR) protein (Miyake et al., 1999 Krishnamurthy and Schuetz, 2006). BCRP is expressed in plasma membrane of placental syncytiotrophoblasts of the chorionic villus (Mao, 2008 Robey et al., 2009), mammary glands, testis, canicular membrane of hepatocytes, cortical and proximal tubules in the kidney, villous tip of intestinal cells in the small intestine, hematopoietic stem cells, endothelial cells of venules and capillaries, and the luminal surface of the endothelial cells at the blood-brain barrier. The substrate specificity for BCRP overlaps broadly with P-gp therefore, the clinical DDI implications for BCRP are as yet not well defined. The current limited data suggest that BCRP may have an impact on chemoresistance in cancer (Noguchi et al., 2009). Rosuvastatin and topotecan have been reported to increase plasma AUC for antivirals and cyclosporins (Allen et al., 2002 Maliepaard et al., 2001, Table 4.8). 

Other drags that suppress hver CYP2C11 and CYP3A2 levels include cyclosporine [203, 204] and chloramphenicol [205], although the latter effects are strain dependent and are associated with a modest reduction in plasma levels of thyroxine but not testosterone [205]. GH does not appear to play a role in the suppression of CYP2C11 and CYP3A2 by cyclosporine, which does not alter the plasma GH peak amplitude, niunber, or duration [206]. Phenobarbital [24, 207, 208], dexa-methasone [28], 5-fluoroiuacil [209], doxorubicin [210], fenofibrate [211], rosuvastatin [212],... 

Adefovir, amlodipine, busulfan, cefaclor, cefdinir, cefixime, citalopram, cyclosporine, fenofibric acid, hydrocodone, hydromorphone, lonafarnib, nalmefene, rosuvastatin voriconazole... 

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