Pharmacokinetics of drugs in adult living donor liver transplant patients: regulatory factors and observations based on studies in animals and humans

Abstract

Introduction: Limited information is available on the pharmacokinetics of drugs in the donors and recipients following adult living donor liver transplantation (LDLT). Given that both the donors and recipients receive multiple drug therapies, it is important to assess the pharmacokinetics of drugs used in these patients.

Areas covered: Pathophysiological changes that occur post-surgery and regulatory factors that may influence pharmacokinetics of drugs, especially hepatic drug metabolism and transport in both LDLT donors and the recipients are discussed. Pharmacokinetic data in animals with partial hepatectomy are presented. Clinical pharmacokinetic data of certain drugs in LDLT recipients are further reviewed.

Expert opinion: It takes up to six months for the liver volume to return to normal after LDLT surgery. In the LDLT recipients, drug exposure generally is higher with lower clearance during early period post-transplant; lower initial dosages of immunosuppressants are used than deceased donor liver transplant recipients during the first six months post-transplantation. In animals, the activities of hepatic drug metabolizing enzymes and transporters are known to be altered differentially during liver regeneration. Future studies on the actual hepatic function with reference to drug metabolism, drug transport, and biliary secretion in both LDLT donors and recipients are required.

Keywords: Cytochromes P450; drug metabolism; drug transporter; liver resection; liver transplant; pro-inflammatory cytokine.