Cyclosporine a-based immunotherapy in adult living donor liver transplantation: Accurate and improved therapeutic drug monitoring by 4-hr intravenous infusion

Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Transplantation (Impact Factor: 3.83). 07/2011; 92(1):100-5. DOI: 10.1097/TP.0b013e31821dcae3
Source: PubMed


A paucity of data exists for evaluating therapeutic drug monitoring in association with clinical outcomes of cyclosporine A (CYA) treatment in living donor liver transplantation (LDLT).
A retrospective cohort analysis was conducted on 50 consecutive adult patients who underwent LDLT between 2001 and 2009 to investigate the feasibility and efficacy of 4-hr continuous intravenous infusion of CYA-based immunotherapy (4-hr CYA-IV, n=27) and compare the pharmacokinetic profile and short-term prognoses with an oral microemulsion formulation of CYA (CYA-ME, n=23).
All patients in the 4-hr CYA-IV group reached target CYA peak by day 3 compared with only 22% in the CYA-ME group (P<0.001). Adjustability to achieve the target range was easier in the 4-hr CYA-IV group compared with the CYA-ME group (P=0.017). Acute cellular rejection rate was lower in the 4-hr CYA-IV group (0%) compared with the CYA-ME group (17%, P=0.038). A subset analysis of the CYA-ME group revealed that CYA exposure was affected by external bile output (P=0.006). Patients in the CYA-ME group showed increased risk of switch to tacrolimus (35%) compared with the 4-hr CYA-IV group (7%, P=0.030). Toxicities and mortality rates were equivalent. The optimal initial dose of oral CYA at conversion from the 4-hr CYA-IV was considered to be 3-fold greater than that of the intravenous dose.
In LDLT, our 4-hr CYA-IV immunosuppression protocol was superior to CYA-ME oral dosing and allowed accurate therapeutic drug monitoring with excellent patient compliance.

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