title: Update and trends on pharmacokinetic studies in patients with impaired renal function: practical insight into application of the FDA and EMA guidelines.
abstract: The incidence of kidney dysfunction increases with age and is highly prevalent among patients with hypertension. Since many therapeutic compounds are primarily eliminated through the kidneys, impaired renal function can have negative consequences on drug disposition, efficacy and safety. Therefore, regulatory agencies such as the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have issued detailed guidelines for new drug applications to determine posology requirements for patients with renal impairment. Areas covered: The current review highlights and contrasts agency requirements for pharmacokinetic renal impairment clinical studies. While many of the guidelines are similar among the two agencies, glomerular filtration rate (GFR) determination and reporting differ. Design considerations for a reduced, full or dialysis renal impairment study, as well as modifications to the FDA's draft guidance are discussed. Furthermore, scenarios where pharmacokinetic modelling analysis can benefit a drug development program are also reviewed. Moreover, practical solutions for patient recruitment challenges are addressed. Expert commentary: We summarize how 'one size does not fit all' for GFR assessment, and recommend when to use certain modalities. Finally, we highlight the need for the pharmaceutical industry to engage therapeutic experts to assist in protocol development for renal impairment studies, as these experts understand the nuances of this special population and recommended guidelines.
authors.affiliation: a Global Clinical Research , Celerion , Phoenix AZ , USA.
authors.forename: Sabina
authors.initials: S
authors.lastname: Paglialunga
authors.affiliation: b Clinical Pharmacology and Pharmacometrics , Celerion , Toronto ON , Canada.
authors.forename: Elliot
authors.initials: E
authors.lastname: Offman
authors.affiliation: c External Study Management , Celerion , Toronto ON , Canada.
authors.forename: Nita
authors.initials: N
authors.lastname: Ichhpurani
authors.affiliation: d Orlando Clinical Research Center , Orlando FL , USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Marbury
authors.affiliation: e Drug Development Services , Celerion , Lincoln NE , USA.
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Morimoto
mesh_terms: D015195:Drug Design; D005060:Europe; D005919:Glomerular Filtration Rate; D006801:Humans; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010599:Pharmacokinetics; D017410:Practice Guidelines as Topic; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000503:physiopathology* / Q000628:therapy; D012307:Risk Factors; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D004364:Pharmaceutical Preparations
keywords: Kidney; chronic kidney disease; clinical studies; drug development; end-stage renal disease; glomerular filtration rate; new drug application