Pharmacokinetics of isotretinoin and its major blood metabolite following a single oral dose to man.
A pharmacokinetic profile of isotretinoin and its major dermatologically active blood metabolite, 4-oxo-isotretinoin, was developed following a single 80 mg oral suspension dose of isotretinoin to 15 normal male subjects. Blood samples were assayed for isotretinoin and 4-oxo-isotretinoin using a newly developed reverse-phase HPLC method. Following rapid absorption from the suspension formulation, isotretinoin is distributed and eliminated with harmonic mean half-lives of 1.3 and 17.4 h, respectively. Maximum concentrations of isotretinoin in blood were observed at 1 to 4 h after dosing. Maximum concentrations of the major blood metabolite of isotretinoin, 4-oxo-isotretinoin, are approximately one-half those of isotretinoin and occur at 6 to 16 h after isotretinoin dosing. The ratio of areas under the curve for metabolite and parent drug following the single dose suggests that average steady-state ratios of metabolite to parent drug during a dosing interval will be approximately 2.5. Both isotretinoin and its metabolite can be adequately described using a single linear pharmacokinetic model.
D000284:Administration, Oral; D000328:Adult; D006801:Humans; D015474:Isotretinoin; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000378:metabolism*
C002202:4-oxoretinoic acid; D014212:Tretinoin; D015474:Isotretinoin