The aim of the study was to investigate the plasma concentrations of i
sotretinoin and its metabolites, at three doses and after single and m
ultiple topicalapplications of isotretinoin gel(0.05%) in hairless rat
s. We used a highly sensitive HPLC method for simultaneous determinati
ons of these compounds, with adetection limit of 2 ng/ml in plasma. Is
otretinoin and its metabolites were detected after single and multiple
cutaneous applications of overdosing (2,000 mg) of isotretinoin gel u
p to 24 h after the single dose and after the last dose. The plasma co
ncentrations of these compounds were below the limit of quantification
in all the animals at all times for the 200- and 20-mg doses.