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.