Monitoring of isotretinoin therapy by measuring the plasma levels of isotretinoin and 4-oxo-isotretinoin. A useful tool for management of severe acne.
BACKGROUND
Isotretinoin for oral therapy in severe acne conglobata and acne nodulocystica represents a significant achievement; however, the drug exerts several mucocutaneous and systemic adverse effects, besides its teratogenic potency.


OBJECTIVE
The aim of this study was to investigate the plasma levels of isotretinoin and of 4-oxo-isotretinoin over long-term treatment of severe acne and to assess any correlation with the given dose, the clinical improvement and the occurrence of side effects.


METHODS
Forty-one patients with severe acne and acne-related disorders were studied under long-term oral intake of isotretinoin. Therapeutic effects and side effects were evaluated prior, during and at the end of therapy. The plasma levels of isotretinoin and of its major metabolite 4-oxo-isotretinoin were measured by reversed-phase HPLC and were correlated with the administered oral dose and the number and frequency of side effects.


RESULTS
Dose-dependent plasma levels of isotretinoin and its metabolite were observed. At a mean dosage of 0.75-1.0 mg/kg/day, 404 +/- 142 ng/ml were measured, whereas the plasma levels of 4-oxo-isotretinoin were 1-2x higher. The plasma levels correlated well with the orally administered dose of isotretinoin and the observed mucocutaneous side effects.


CONCLUSIONS
The study demonstrates that measuring of the plasma levels may be a helpful tool to monitor the individual therapeutic dose regimen in patients with severe acne in order to minimize undesired side effects and to control oral intake.
Almond-Roesler
B
B
Department of Dermatology, University Medical Center Benjamin Franklin, Free University of Berlin, Germany.
Blume-Peytavi
U
U
Bisson
S
S
Krahn
M
M
Rohloff
E
E
Orfanos
C E
CE
D000152:Acne Vulgaris / Q000188:drug therapy* / Q000378:metabolism; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D015474:Isotretinoin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000097:blood
C002202:4-oxoretinoic acid; D014212:Tretinoin; D015474:Isotretinoin