Novatretin Mechanism of Action





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Full Prescribing Info
Pharmacology: Acitretin, the active ingredient of NOVATRETIN, is a synthetic aromatic analogue of retinoic acid. In preclinical investigations of the tolerability of acitretin, no relevant mutagenic or carcinogenic effects were found, nor was there any evidence of direct liver toxicity. Acitretin was found to be highly teratogenic in animals.
Clinical trials confirmed that, in psoriasis and disorders of keratinization, acitretin brought about normalization of epidermal cell proliferation, differentiation and cornification, while the side effects were, in general, tolerable. The effect of acitretin is purely symptomatic; the mechanism of action is as yet largely unknown.
Pharmacokinetics: Absorption: Acitretin reaches peak plasma concentration 1-4 hours after ingestion of the medicine. Bioavailability of orally administered acitretin is best when the medicine is taken together with food. Bioavailability of a single dose is approximately 60%, but this may vary considerably from one patient to another (36-95%).
Distribution: Acitretin is highly lipophilic and penetrates readily into body tissues. Protein binding of acitretin exceeds 99%. In animal studies, acitretin passed the placental barrier in quantities sufficient to produce foetal malformations. Due to its lipophilic nature, it can be assumed that acitretin passes into breast milk in considerable quantities.
Metabolism: Acitretin is metabolized by isomerization into its 13-cis isomer (cis acitretin), by glucuronidation and cleavage of the side chain.
Elimination: Multiple-dose studies in patients aged 21-70 years showed an elimination half-life of approximately 50 hours for acitretin and 60 hours for its main metabolite in plasma, cis acitretin, which is also a teratogen. From the longest elimination half-life observed in these patients for acitretin (96 hours) and cis acitretin (123 hours), and assuming linear kinetics, it can be predicted that more than 99% of the medicine is eliminated within 36 days after cessation of long-term therapy. Furthermore, plasma concentrations of acitretin and cis acitretin dropped below the sensitivity limit of the assay (<6 ng/ml) within 36 days following cessation of treatment. Acitretin is excreted entirely in the form of its metabolites, in approximately equal parts via the kidneys and the bile.
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