Cyclosporine pharmacokinetics in anti‐HCV+ patients

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Abstract
Abstract: Background: Cyclosporine (CsA) is a widely used immunosuppressive agent in kidney transplant patients. In Brazil, around 30% of patients awaiting kidney transplantation carry anti‐HCV antibodies. Previous observations suggest altered CsA pharmacokinetics in these patients.Methods: We conducted two pharmacokinetic studies. In the pre‐transplant (pre‐Tx) study, we examined 22 dialysis patients on chronic hemodialysis awaiting transplantation, 11 anti‐HCV+ [seven polymerase chain reaction (PCR)‐positive] matched against 11 controls. In the post‐transplant (post‐Tx) study, we enrolled 24 kidney allograft recipients – 10 anti‐HCV+ (six PCR‐positive), and 14 controls. In the first study, all patients received an 8‐mg/kg dose of CsA microemulsion (ME). Secondly, the dosage was indicated by the patient's medical team. Pharmacokinetic parameters were calculated from 13 blood samples (0–12 h postdose) by fluorescence polarization immunoassay with specific monoclonal antibodies.Results: In both studies, maximum concentration (Cmax), minimum concentration (Cmin) and area under the CsA time–concentration curve from 0 to 12 h (AUC0−12) were higher for anti‐HCV+ patients than for controls, but significantly so only forAUC0−12in the pre‐Tx study (42%; p < 0.05). When PCR‐positive patients were compared with controls, differences were amplified. In the pre‐Tx study, differences were 58%, 69%, and 91% higher in PCR‐positive patients forCmax(p = 0.05),AUC0−12(p < 0.01), andCmin(p < 0.01), respectively. In the post‐Tx study, results were 50% (p < 0.01) and 32% (p < 0.01) higher in PCR‐positive patients forCmaxandAUC0−12, respectively. In the pre‐Tx study, the impact of viremia was significantly higher in female patients. CsA trough levels remained higher along the first year post‐transplantation in viremic patients.Conclusions: Anti‐HCV+ patients, especially those with viremia, present altered CsA pharmacokinetics, with higher peak levels and drug exposure than controls.