Monitoring of Isotretinoin Therapy by Measuring the Plasma Levels of Isotretinoin and 4-Oxo-Isotretinoin

Abstract

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-oxoisotretinoin 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 1–2 × higher. The plasma levels correlated well with the orally administered dose of isotretinoin and the observed mucocutaneous side effects. Conclusion: 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.

Isotretinoin and the Risk of Depression in Patients With Acne Vulgaris

“…It has been proposed that twice daily dosing regimens of the drug can decrease the appearance 0f side effects (132).…”

“…Interestingly, the absence of cheilitis during the treatment may be an indicator 0f non-compliance (132). Other mucocutaneous side effects have been reports of the thinning cf the hair and increased brittleness of the nails.…”

Oral Retinoids in the Treatment of Seborrhoea and Acne

“…Since the frequency of cheilitis is nearly 100%, its appearance 2–3 weeks after inititiation of treatment is regarded as a marker for sufficient absorption. In patients receiving 0.5–1.0 mg/kg/day with a lack of or insufficient clinical response to therapy and who have not experienced mucocutaneous adverse effects, blood concentration monitoring is recommended to ensure absorption [50]. …”

“…HPLC is the method of choice for highly sensitive (as low as 2 ng/ml) and selective isotretinoin detection and measurements [50]. If traces of isotretinoin are detected, interruption of pregnancy is recommended.…”

Les génériques mettent-ils les patients en danger?

“…La concentration plasmatique de l'isotréti-noïne et de son métabolite principal, le 4-oxoisotrétinoïne, est dose-dépendante, mais elle varie cependant fortement entre les individus. Ainsi, les taux d'isotrétinoïne après administration répétée du même produit à la dose de 0,75-1,0 mg/kg se distingue d'un facteur 6, ceux du 4-oxo-isotrétinoïne d'un facteur 3 [9]. Cette variabilité pourrait être due à une biodisponibilité variable et à des différences interindividuelles dans l'activité des enzymes qui mé-tabolisent la substance-mère.…”