title: Human variability in the renal elimination of foreign compounds and renal excretion-related uncertainty factors for risk assessment.
abstract: Renal excretion is an important route of elimination for xenobiotics and three processes determine the renal clearance of a compound [glomerular filtration (about 120 ml/min), active renal tubular secretion (>120 ml/min) and passive reabsorption (<120 ml/min)]. Human variability in kinetics has been quantified using a database of 15 compounds excreted extensively by the kidney (>60% of a dose) to develop renal-excretion related uncertainty factors for the risk assessment of environmental contaminants handled via this route. Data were analysed from published pharmacokinetic studies (after oral and intravenous dosing) in healthy adults and other subgroups using parameters relating primarily to chronic exposure [renal and total clearances, area under the plasma concentration time-curve (AUC)] and acute exposure (Cmax). Interindividual variability in kinetics was low for both routes of exposure, with coefficients of variation of 21% (oral) and 24% (intravenous) that were largely independent of the renal processes involved. Renal-excretion related uncertainty factors were below the default kinetic uncertainty factor of 3.16 for most subgroups analysed with the exception of the elderly (oral data) and neonates (intravenous data) for whom renal excretion-related factors of 4.2 and 3.2 would be required to cover up to 99% of these subgroups respectively.
authors.affiliation: School of Medicine, University of Southampton, Biomedical Sciences Building, Bassett Crescent East, SO16 7PX Southampton, UK.
authors.forename: J L C M
authors.initials: JL
authors.lastname: Dorne
authors.forename: K
authors.initials: K
authors.lastname: Walton
authors.forename: A G
authors.initials: AG
authors.lastname: Renwick
mesh_terms: D000284:Administration, Oral; D019540:Area Under Curve; D005503:Food Additives / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005919:Glomerular Filtration Rate; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000378:metabolism*; D012016:Reference Values
chemical_list: D005503:Food Additives