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.
Keywords: Cyclosporine, tacrolimus, sirolimus, mycophenolic acid, factors of variability, pharmacokinetic, kidney
transplant patients, population model.
Rights & PermissionsPrintExport