Factors Affecting the Pharmacokinetics after Living Donor Liver Transplant

Abstract

Fifty-five thousand organ transplants are performed each year around the world. It is now estimated that over 300,000 organ transplant recipients are alive worldwide. Most of these transplant recipients will remain on immunosuppressive drugs for the remainder of their lives to prevent rejection episodes. Doses of these medications must be judiciously managed to optimize patient outcomes. Subtherapeutic drug concentrations may lead to graft rejection and subsequent graft loss. Supratherapeutic drug concentrations increase the likelihood of drug toxicities and increase the likelihood of opportunistic infections. In this review, the latest reports concerning the factors affecting the pharmacokinetics of tacrolimus and micafungin after living donor liver transplant (LDLT) are summarized. Our experimental results demonstrate that preoperative assessment of cytochrome P450 3A5 (CYP3A5) genotypes in both recipients and donors and an immune cell function assay would be useful not only for predicting tacrolimus pharmacokinetics but also for defining groups at high-risk of infectious complications after LDLT. Finally, monitoring plasma trough micafungin concentrations allows safe and effective dose titration of micafungin in LDLT-recipients with total bilirubin concentrations greater than 5 mg/dL.