Factors influencing the cyclosporine clearance

in allogeneic hematopoietic cell transplant recipients

Yeon Joo Lee , Seong Gil ° Ryu, Jae Youn Kim, Hye Young Shin

Department of Pharmacy, Asan Medical Center

Background : cyclosporine(CsA) has been the most extensively used immunosuppressive agent to prevent or treat graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation(HCT). Because of the severity of the adverse reaction and the pharmacokinetic complexity of CsA, maintaining the optimal therapeutic CsA concentration is mandatory to promote engraftment and to avoid toxicity. Unfortunately, there are no reports that have evaluated the correlation between CsA pharmacokinetics and dose adjustment in HCT. Then the objective of our study is to evaluate the factors that alter the clearances of CsA in HCT recipients.

Method : This study was conducted in 47 patients who underwent allogeneic HCT in Asan Medical Center during January 2004~June 2006. We retrospectively analyzed the factors of each patients during 60 days after HCT. The clearance of CsA was evaluated by using cKin 1.1*. Then we evaluated the correlation between clearance and factorsusing SPSS version 12.0. The used statistical methods were non-parametric Mann-Whitney’s u-test, spearman's correlation and multiple linear regression for univariate and multivariate analysis.

Result : The mean clearance(CL)±s.d. of CsA was 26.64±8.38 L/hr (0.49±0.15L/hr/kg). Experience of veno-occlusive disease and elevation of total bilirubin(t-bil) was significantly related to decreased CsA clearance (P=0.012, P=0.016). In multivariate analysis, the most significant factor for CsA clearance was t-bil(P=0.008).

Conclusion : The Influence of elevated t-bil to CsA clearance suggests that the close monitoring of CsA blood level in hepatic dysfunction patients is required to obtain optimal therapeutic outcome.