title: Pharmacokinetics of drugs in adult living donor liver transplant patients: regulatory factors and observations based on studies in animals and humans.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Pharmaceutical Sciences, School of Pharmacy , University of Pittsburgh , Pittsburgh , PA , USA.|b School of Medicine , Tsinghua University , Beijing , China.
authors.forename: Mi
authors.initials: M
authors.lastname: Li
authors.affiliation: a Department of Pharmaceutical Sciences, School of Pharmacy , University of Pittsburgh , Pittsburgh , PA , USA.|c Office of Pharmaceutical Quality , Center for Drug Evaluation and Research, US Food and Drug Administration , Silver Spring , MD , USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: d Department of Surgery, School of Medicine , Thomas Starzl Transplantation Institute , Pittsburgh , PA , USA.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Humar
authors.affiliation: d Department of Surgery, School of Medicine , Thomas Starzl Transplantation Institute , Pittsburgh , PA , USA.
authors.forename: Amit D
authors.initials: AD
authors.lastname: Tevar
authors.affiliation: d Department of Surgery, School of Medicine , Thomas Starzl Transplantation Institute , Pittsburgh , PA , USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Hughes
authors.affiliation: a Department of Pharmaceutical Sciences, School of Pharmacy , University of Pittsburgh , Pittsburgh , PA , USA.|d Department of Surgery, School of Medicine , Thomas Starzl Transplantation Institute , Pittsburgh , PA , USA.|e Magee Womens Research Institute , Pittsburgh , PA , USA.|f Department of Pathology , School of Medicine, University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Raman
authors.initials: R
authors.lastname: Venkataramanan
mesh_terms: D000328:Adult; D000818:Animals; D006498:Hepatectomy / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D016031:Liver Transplantation / Q000379:methods; D019520:Living Donors; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism; D010599:Pharmacokinetics; D066027:Transplant Recipients
chemical_list: D007166:Immunosuppressive Agents; D004364:Pharmaceutical Preparations
keywords: Cytochromes P450; drug metabolism; drug transporter; liver resection; liver transplant; pro-inflammatory cytokine