Effect of simvastatin on cyclosporine unbound fraction and apparent blood clearance in heart transplant recipients
Abstract
To investigate the effects of lipid lowering therapy on the fraction unbound and dosage requirement of cyclosporine in heart transplant recipients. Cyclosporine fraction unbound (fu) was measured ex vivo in plasma obtained from heart transplant recipients (n=12) before and after lipid lowering treatment, using equilibrium dialysis. Cyclosporine trough concentration data were also collected from cardiac transplant recipients (n=32) who received simvastatin for the treatment of hyperlipidaemia. Cyclosporine daily dosage and total concentration (monoclonal FPIA method) were recorded for periods up to 6 months before and after simvastatin administration. The total number of dose rate-concentration observations was 172 before and 135 after simvastatin administration respectively. Using a population pharmacokinetic approach (implemented in P-PHARM software) the ratio of dose rate to trough concentration at steady state (DR/C[SS trough]), an estimation of apparent clearance, was determined. The posterior Bayesian estimate of DR/C(SS trough) was calculated for each patient before and after simvastatin administration. The mean fu increased by 29%, from 1.40 +/- 0.1% (mean +/- s.d.) to 1.82 +/- 0.22% after simvastatin administration (P <...Continue Reading
Citations
Ezetimibe in renal transplant patients with hyperlipidemia resistant to HMG-CoA reductase inhibitors
Related Concepts
Related Feeds
ApoE, Lipids & Cholesterol
Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.