title: Need for reduction of cyclosporin dosage in renal transplant patients with hypertriglyceridemia but not hypercholesterolemia.
abstract: Currently there is a paucity of data regarding the influence of high serum triglyceride levels on cyclosporin A (CyA) levels and dosing. We therefore undertook a retrospective study to determine the relationship of serum lipid levels to CyA levels and CyA dosages. Renal transplant patients at a 0.5-to-3-year post-transplant stage, with a stable CyA dosage, who were not on medications that affect CyA metabolism or renal function, were entered into the study. The CyA dosage was adjusted by clinicians to maintain whole blood. 12-h CyA trough levels between 200 and 250 ng/ml (monoclonal TDX method, which measures the parent compound). Forty-four patients qualified for the study. The data clearly indicated that high cholesterol levels (> 300 mg/dl and with normal triglyceride levels) did not influence the CyA levels or the dosages. Conversely, high triglyceride levels ( > 500 mg/dl) significantly reduced the amount of CyA required. A decreased clearance of CyA in the presence of hypertriglyceridemia led to high CyA levels in some patients. Reducing the CyA dosage to achieve levels between 200 and 250 ng/ml improved renal allograft function and decreased other side effects attributed to CyA toxicity. These studies indicate that high triglyceride levels, but not high cholesterol levels, increase CyA levels, which can lead to CyA toxicity.
authors.affiliation: Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
authors.forename: F G
authors.initials: FG
authors.lastname: Porres
authors.forename: W C
authors.initials: WC
authors.lastname: Stevenson
authors.forename: C
authors.initials: C
authors.lastname: McCullough
authors.forename: T L
authors.initials: TL
authors.lastname: Pruett
authors.forename: P I
authors.initials: PI
authors.lastname: Lobo
authors.forename: N
authors.initials: N
authors.lastname: Nezamuddin
mesh_terms: D000293:Adolescent; D002784:Cholesterol / Q000097:blood*; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000517:prevention & control*; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood* / Q000188:drug therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000276:immunology*; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D002784:Cholesterol; D003404:Creatinine