IngentaConnect Cyclosporine pharmacokinetics in anti-HCV+ patients

Abstract:

Wolffenbüttel L, Poli DD, Manfro RC, Gonçalves LFS. Cyclosporine pharmacokinetics in anti-HCV+ patients.

Clin Transplant 2004 DOI: 10.1111/j.1399-0012.2004.00256.x © Blackwell Munksgaard, 2004 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 (C_max), minimum concentration (C_min) 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 for AUC₀₋₁₂ in 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 for C_max (p = 0.05), AUC₀₋₁₂ (p < 0.01), and C_min (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 for C_max and AUC₀₋₁₂, 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.

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