title: The complete pharmacokinetic profile of serum cardiac troponin I in the rat and the dog.
abstract: Recent improvements in assays have allowed serum cardiac troponin I (cTnI) to be measured at previously undetectable concentrations, which may have implications for cardiotoxicity studies. We characterized the pharmacokinetics of cTnI after a single iv administration of purified cTnI in rats at doses of 0.005, 0.05, and 0.5 μg/kg and in beagle dogs at doses of 0.05, 0.1, and 0.2 μg/kg. Serum cTnI concentration-time profiles were well described by a two-compartment pharmacokinetic model with first-order elimination in both species. The estimated mean (SD) values of total serum clearance, volume of distribution of the central compartment, and terminal half-life were 318 ml/h/kg, 52.9 ml/kg, and 0.8 h in rats and 481 (135) ml/h/kg, 230 (70) ml/kg, and 1.85 (0.5) h in dogs, respectively. In both species, a fast distribution phase was followed by a relatively slow elimination phase. These data indicate that the current practice in cardiotoxicity studies of unguided blood sampling should be revised. A targeted case-by-case approach is required whereby samples are collected not only relative to the kinetics of the test article but also in relation to the kinetics of the biomarker in the test species and the type and severity of anticipated cardiovascular perturbation. This approach is essential for the identification of subtle increases of serum cTnI concentrations in the low dynamic range.
authors.affiliation: Department of Non-Clinical Safety, Hoffmann-La Roche, Inc., Nutley, New Jersey 07110, USA. michael.dunn.md1@roche.com
authors.forename: Michael E
authors.initials: ME
authors.lastname: Dunn
authors.forename: Denise
authors.initials: D
authors.lastname: Coluccio
authors.forename: Gerard
authors.initials: G
authors.lastname: Hirkaler
authors.forename: Igor
authors.initials: I
authors.lastname: Mikaelian
authors.forename: Rosemary
authors.initials: R
authors.lastname: Nicklaus
authors.forename: Steven E
authors.initials: SE
authors.lastname: Lipshultz
authors.forename: Lucette
authors.initials: L
authors.lastname: Doessegger
authors.forename: Micaela
authors.initials: M
authors.lastname: Reddy
authors.forename: Thomas
authors.initials: T
authors.lastname: Singer
authors.forename: Wanping
authors.initials: W
authors.lastname: Geng
mesh_terms: D000818:Animals; D004285:Dogs; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D019210:Troponin I / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D019210:Troponin I