title: Plasma concentration profiles of simvastatin 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitory activity in kidney transplant recipients with and without ciclosporin.
abstract: A few cases of severe rhabdomyolysis have been reported in heart transplant recipients treated simultaneously with ciclosporin (CS) and the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor lovastatin. When measured, plasma lovastatin HMG-CoA reductase inhibitor concentrations in these patients were higher than expected. This prompted us to study the plasma concentration profiles of simvastatin HMG-CoA reductase inhibitory activity after a single dose of simvastatin in kidney transplant recipients. Five patients treated with CS, azathioprine and prednisolone (CS patients) were compared to 5 patients treated with azathioprine and prednisolone (non-CS patients). The concentration curves had similar shapes but the mean area under the curve/24 h was almost 3 times higher (p = 0.047) and the mean peak concentration was twice as high in CS patients (p = 0.028). These results suggest a difference in the disposition of simvastatin in CS patients as compared to non-CS patients. Simvastatin should be administered in a reduced dosage to CS patients.
authors.affiliation: Department of Nephrology, University Hospital, Lund, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Arnadottir
authors.forename: L O
authors.initials: LO
authors.lastname: Eriksson
authors.forename: H
authors.initials: H
authors.lastname: Thysell
authors.forename: J D
authors.initials: JD
authors.lastname: Karkas
mesh_terms: D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000502:physiology; D008148:Lovastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D012206:Rhabdomyolysis / Q000139:chemically induced; D019821:Simvastatin
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016572:Cyclosporine; D008148:Lovastatin; D019821:Simvastatin