Knowledge of inter-strain and inter-gender differences in drug metabolism 
studies is important for animal selection in pharmacokinetic and toxicological 
studies. The effects of rat strain and gender in in vitro metabolism were 
investigated in Sprague Dawley (SD) and Wister Han (WH) rats based on the 
hepatocyte metabolic profiles of 14 small molecule drugs. Similarities were 
found between the hepatocyte metabolic clearances of SD and WH strains, 
suggesting that only one strain can be confidently used for the evaluation of 
hepatic clearance. Neither strain of rat was preferable over the other to cover 
human metabolites. Higher similarities in metabolic pathways were found between 
the same gender than the same strain. Differences in metabolite identities, 
metabolite formation rates and potential biotransformation pathways were 
observed between SD and WH rat strains. Eleven metabolites from six drugs were 
"disproportionally" formed between SD and WH rats. The use of a specific rat 
strain model and gender for ADME and toxicity testing should, therefore, be 
carefully considered as metabolic profiles may differ, even though metabolic 
clearance was similar between SD and WH rats.