Cyclosporine A-based immunotherapy in adult living donor liver transplantation: accurate and improved therapeutic drug monitoring by 4-hr intravenous infusion.
ABSTRACT 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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ABSTRACT: The enduring success of lung transplantation is built on the use of immunosuppressive drugs to stop the immune system from rejecting the newly transplanted lung allograft. Most patients receive a triple-drug maintenance immunosuppressive regimen consisting of a calcineurin inhibitor, an antiproliferative and corticosteroids. Induction therapy with either an antilymphocyte monoclonal or an interleukin-2 receptor antagonist are prescribed by many centres aiming to achieve rapid inhibition of recently activated and potentially alloreactive T lymphocytes. Despite this generic approach acute rejection episodes remain common, mandating further fine-tuning and augmentation of the immunosuppressive regimen. While there has been a trend away from cyclosporine and azathioprine towards a preference for tacrolimus and mycophenolate mofetil, this has not translated into significant protection from the development of chronic lung allograft dysfunction, the main barrier to the long-term success of lung transplantation. This article reviews the problem of lung allograft rejection and the evidence for immunosuppressive regimens used both in the short- and long-term in patients undergoing lung transplantation.Drugs 10/2013; 73(16). DOI:10.1007/s40265-013-0136-x · 4.13 Impact Factor
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ABSTRACT: The choices and extent of immunosuppression critically affect subsequent infection and rejection profiles after lung transplantation (LTx). Evidence does not support a particular induction strategy. Typically, a three drug regimen of a calcineurin inhibitor, cell cycle inhibitor, and corticosteroids provide LTx maintenance immunosuppression. Other agents (including mTOR inhibitors), and other routes of administration (sublingual or inhaled) tend to be held back for specific clinical problems. Treatment of acute cellular rejection with high dose corticosteroids is usually successful. By contrast, treatment of antibody–mediated rejection is problematic. It requires a combination of high dose corticosteroids, plasmapheresis, rituximab, and intravenous immunoglobulin. Chronic lung rejection is a particular challenge to treat. It is generally stated that any change in immunosuppression can lead to an apparent stabilization. Azithromycin and statins have some efficacy when used early. The current review aims to highlight the rationale for current immunosuppressive choices and draw attention to recent trends and developments.09/2014; 3(3). DOI:10.1007/s13665-014-0081-5