High intra-individual variability of cyclosporine pharmacokinetics in lung transplant recipients without cystic fibrosis

Abstract

Background: There has been little study on the variability of CsA pharmacokinetics in stable lung transplant (LT) recipients without cystic fibrosis. This study was conducted to determine the prevalence of high intra-individual variability of CsA in LT recipients and its implications in CsA monitoring.

Methods: Twenty-nine pharmacokinetic curves were performed in 10 consecutive stable patients from a single center. The intra-individual coefficient of variation (CV) of the AUC₀₋₁₂ h was calculated in each case. Patients were grouped according to whether their CV was high (≥20%) or low (<20%). Correlations between cyclosporine CsA concentration at each time point, AUC₀₋₄ h , and AUC₀₋₁₂ h were also calculated.

Results: Six (60%) patients presented low CVs and four (40%) high CVs. In patients with low CVs, the best correlation of AUC₀₋₁₂ h was with CsA concentration at two h post-dose (C₂) (r = 0.674, p = 0.002), whereas in those with high CV, the best correlation was with C5 (r = 0.800, p = 0.003). In the latter group, the correlation with C₂ was low (r = 0.327, p = 0.32), whereas the correlation with C₀ was high (r = 0.709, p < 0.05).

Conclusions: Intra-individual variability of CsA pharmacokinetics may be high in many LT recipients. In patients with high CV, the use of C₀ levels may be more appropriate for CsA monitoring than C₂ levels.

Keywords: cyclosporine; immunosuppression; intra-individual variability; lung transplantation; pharmacokinetics.