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

Article highlights

• Pathophysiological changes post-transplant, the size of the liver graft/remnant liver in the recipient/donor, polymorphism of metabolizing enzymes/transporters, side effects of immunosuppressants may alter drug pharmacokinetics in both the donor and the recipient.

• Activities of drug metabolizing enzymes and transporters are altered differentially during liver regeneration and impacted by inflammatory cytokines.

• Studies using animals with partial hepatectomy as well as in vitro cell cultures are useful to elucidate the influence of regenerative and inflammatory mechanisms post-liver resection on drug metabolism.

• Lower initial dosages of immunosuppressants should be considered for LDLT recipients compared with those for DDLT recipients during the initial period of liver regeneration. Further studies to elucidate the hepatic drug metabolism and transport, as well as the biliary secretory function in LDLT patients are necessary.

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Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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