title: Population Pharmacokinetic Approach of Immunosuppressive Therapy in Kidney Transplant Patients.
abstract: Immunosuppressive therapy is the cornerstone of successful kidney transplantation. Frequently used immunosuppressives are cyclosporine, tacrolimus, sirolimus and mycophenolic acid. These drugs have narrow therapeutic index and show high pharmacokinetic variability. In order to maintain the balance between efficacy and safety, dosing is based on measured drug concentrations. Proper identification, quantification and understanding the sources of variability in measured concentrations facilitate routine dose adjustment in clinical practice. Classical pharmacokinetic studies have limited use in transplant patients attributable to design with intense sampling in a small, relatively homogenous population, and identification of only single variability factor per study. Population approach is a powerful tool for analysing sparse data, identifying factors that influence drug pharmacokinetics and estimating variability. In this report we reviewed available population pharmacokinetic models for cyclosporine, tacrolimus, sirolimus and mycophenolic acid in adult kidney transplant patients. The major focus was to describe various demographic factors, biochemical parameters, genetic polymorphisms of metabolic enzymes and transporters and drug-drug interactions, which have been identified as an important concern of pharmacokinetic variability in kidney transplant patients.
authors.forename: Bojana
authors.initials: B
authors.lastname: Golubovic
authors.forename: Milica
authors.initials: M
authors.lastname: Prostran
authors.affiliation: Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, Serbia, Vojvode Stepe 450, 11221 Belgrade. branislava.miljkovic@pharmacy.bg.ac.rs.
authors.forename: Branislava
authors.initials: B
authors.lastname: Miljkovic
authors.forename: Katarina
authors.initials: K
authors.lastname: Vucicevic
authors.forename: Dragana
authors.initials: D
authors.lastname: Radivojevic
authors.forename: Iztok
authors.initials: I
authors.lastname: Grabnar
mesh_terms: D016572:Cyclosporine / Q000493:pharmacokinetics / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control*; D006207:Half-Life; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016030:Kidney Transplantation; D009173:Mycophenolic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use; D020123:Sirolimus / Q000493:pharmacokinetics / Q000627:therapeutic use; D016559:Tacrolimus / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus