Short-term increase of serum troponin I and serum heart-type fatty acid-binding protein (H-FABP) in dogs following administration of formoterol.
In this paper, changes in serum levels of the cardiac biomarkers troponin I and the heart-type fatty acid-binding protein (H-FABP) following administration of a long-acting beta(2)-sympathicomimeticum (long-acting beta-agonist, LABA) to dogs were measured. We measured troponin I in dogs in a 4-week repeated-dose study with inhalative administration of formoterol (13microg/kgd) and a glucocorticoid/formoterol combination (143/16microg/kgd). The medians of troponin I increased within 3 days in both groups, far beyond the cut-off level (0.1microg/L), but returned to baseline levels on study day 9. The increase was more pronounced in the formoterol-only group (3.29microg/L) compared to the glucocorticoid/formoterol combination group (1.32microg/L). In a second study, we measured serum troponin I as well as serum H-FABP levels in several samples over 7 days in dogs, receiving a single inhalative dose of a glucocorticoid/formoterol combination (120/12mug/kgd). The median of the troponin I concentration increased above the cut-off level within 2h and that of H-FABP within 4h. The medians of both parameters were temporarily above the cut-off levels even on study day 7. Both studies were conducted according to national animal welfare guidelines. To our knowledge, this is the first report that shows a corresponding increase of troponin I and H-FABP in dogs treated with formoterol. Both parameters are more sensitive in detecting a drug-induced cardiac injury compared to total LDH, total CK as well as CK MB activity. However, it is recommended to take at least three blood samples per day to assess a temporary increase of troponin I.
Strauss
Volker
V
Institute of Preclinical Drug Safety, Nycomed GmbH, Hamburg, Germany.
Wöhrmann
Thomas
T
Frank
Ilona
I
Hübel
Ulrich
U
Luft
Jörg
J
Bode
Gerd
G
Germann
Paul-Georg
PG
D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002940:Circadian Rhythm; D003692:Delayed-Action Preparations; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects*; D050556:Fatty Acid-Binding Proteins / Q000097:blood*; D005260:Female; D000068759:Formoterol Fumarate; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000139:chemically induced; D013997:Time Factors; D019210:Troponin I / Q000097:blood*
D058666:Adrenergic beta-2 Receptor Agonists; D015415:Biomarkers; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D004983:Ethanolamines; D050556:Fatty Acid-Binding Proteins; D005938:Glucocorticoids; D019210:Troponin I; D000068759:Formoterol Fumarate