title: Serum transaminase levels should be measured immediately prior to dosing in early phase I clinical trials.
abstract: Observations of predose spikes in transaminases from a phase I study prompted our review of other clinical trials, including 250 healthy participants from 4 studies at 3 sites. Six of these participants (2.4%) displayed elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST) levels immediately predose despite normal values <48 hours previously, including one with ALT/AST = 237/175 IU/L (previously 41/29 IU/L). Testing immediately prior to dosing can exonerate a study drug and avoid unnecessary, expensive delays in early clinical trials.
authors.affiliation: The Ohio State University College of Medicine, Department of Pharmacology, 5072-B Graves Hall, 333 West 10th Avenue, Columbus, OH 43210-1239, USA. david.groen@osumc.edu
authors.forename: David
authors.initials: D
authors.lastname: Groen
authors.forename: Stephen
authors.initials: S
authors.lastname: Harris
authors.forename: Salvatore
authors.initials: S
authors.lastname: Colucci
authors.forename: Glen
authors.initials: G
authors.lastname: Apseloff
mesh_terms: D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D001219:Aspartate Aminotransferases / Q000097:blood*; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis; D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D005260:Female; D006801:Humans; D008111:Liver Function Tests / Q000379:methods; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D055815:Young Adult
chemical_list: D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase