The complete pharmacokinetic profile of serum cardiac troponin I in the rat and the dog

Michael E. Dunn, Denise Coluccio, Gerard Hirkaler, Igor Mikaelian, Rosemary Nicklaus, Steven E. Lipshultz, Lucette Doessegger, Micaela Reddy, Thomas Singer, Wanping Geng

Research output: Contribution to journalArticle

31 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)368-373
Number of pages6
JournalToxicological Sciences
Volume123
Issue number2
DOIs
StatePublished - Oct 1 2011

Keywords

  • Biomarker
  • Cardiac troponin I
  • Dog
  • Kinetics
  • Rat
  • Ultrasensitive assay

ASJC Scopus subject areas

  • Toxicology

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    Dunn, M. E., Coluccio, D., Hirkaler, G., Mikaelian, I., Nicklaus, R., Lipshultz, S. E., Doessegger, L., Reddy, M., Singer, T., & Geng, W. (2011). The complete pharmacokinetic profile of serum cardiac troponin I in the rat and the dog. Toxicological Sciences, 123(2), 368-373. https://doi.org/10.1093/toxsci/kfr190