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Longitudinal studies of cardiac troponin I concentrations in serum from male cynomolgus monkeys: resting values and effects of oral and intravenous dosing on biologic variability
Author(s) -
Schultze Albert Eric,
Anderson Jason M.,
Kern Tom G.,
Justus Ryan W.,
Lee HsiuYung Cindy,
Zieske Lynn R.,
Goodson Robert James,
Florey Sara Hudson
Publication year - 2015
Publication title -
veterinary clinical pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 51
eISSN - 1939-165X
pISSN - 0275-6382
DOI - 10.1111/vcp.12272
Subject(s) - dosing , troponin i , blood sampling , medicine , pharmacology , pharmacokinetics , anesthesia , myocardial infarction
Background There is a paucity of information regarding cardiac troponin ( cT n) concentrations in peripheral blood of nonhuman primates ( NHP ). Even less is known regarding cT n concentrations in monkeys that are restrained for oral or intravenous (iv) dosing. Objectives The objectives of these studies were to (1) determine cardiac troponin I ( cTnI ) concentration in resting Cynomolgus monkeys and investigate biologic variability in cTnI concentration over time, (2) determine cTnI changes in restrained monkeys given sham oral dosing, and (3) determine cTnI changes in restrained NHP given a sham intravenous dosing. Methods The Research Use Only Erenna cTnI ultrasensitive immunoassay based on single molecule counting technology was used to determine serum cTnI concentration in longitudinal studies of male Cynomolgus monkeys at rest, and after sham oral and intravenous dosing. Animals were catheterized prestudy, and blood samples were collected by an automated sampling device to limit disturbance of the animals during studies. Results In resting monkeys cTnI concentrations were relatively low and constant and ranged from 0.2 to 9.6 pg/mL (mean = 2.5 pg/ mL ), with minimal variability during a 24‐hour period. Animals given sham oral dosing also had low cTnI concentration with little variability similar to the resting values. Several animals restrained for intravenous dosing had a small transient increase in cTnI concentration (~5–25 pg/ mL ) that resolved quickly within one to 3 hours postinjection. Conclusions Results of this longitudinal study provide information that may be important in differentiating effects of animal handling from those associated with compound‐related effects in preclinical toxicology studies of drugs in development.