Mechanism of Action
When treating leprosy, dapsone is bacteriostatic against Mycobacterium leprae at 1 to 10 mg/L. Dapsone inhibits the folic acid pathway by preventing the bacteria from utilizing para-aminobenzoic acid (PABA) to synthesize folic acid by competitively antagonizing PABA. Dapsone is also a competitive inhibitor of dihydropteroate synthase.[4]
By treating conditions with neutrophilic infiltrates in the skin, the drug exerts therapeutic activity by affecting neutrophilic functions. Dapsone inhibits the myeloperoxidase-peroxide halide-mediated cytotoxic system, a component of the neutrophil respiratory burst. Through this mechanism, dapsine controls the degree of neutrophil-induced destruction in lesions. In leprosy treatment, dapsone exerts the therapeutic effect by inhibiting the folic acid pathway. It also may inhibit the synthesis of chemotactic lipids and interfere with leukotriene (LTB4) mediated chemotaxis in neutrophils and migration to lesions. Dapsone also decreases the adhesion of neutrophils to IgA.[5]
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Though the actual mechanism of action of dapsone is unknown for dermatologic conditions, the drug does affect human neutrophils, perhaps by moderating the level of damage by neutrophils at the site of lesions and by reducing neutrophil migration to those locations.
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Dapsone may also exert activity on eosinophils and monocytes. The efficacy of the drug in conditions like granuloma annulare and eosinophilic cellulitis, in which monocytes and eosinophils have significant roles, respectively, points to this hypothesis.
The mechanism of topical dapsone in treating acne vulgaris is unknown.
Pharmacokinetics
Pharmacokinetic factors for oral dapsone are as follows:
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Absorption: Orally ingested dapsone is rapidly and nearly completely absorbed. Dapsone is detectable a few minutes following ingestion and reaches peak concentration in 4 to 8 hours.
Distribution: The drug’s volume of distribution is estimated at 1.5 L/kg.[6]
Metabolism: The plasma half-life varies between individuals from 10 to 50 hours, with an average of 28 hours. Repeat tests on the same patient return consistent results. Dapsone is hepatically metabolized by the CYP450 enzyme system, specifically CYP2E1, and it is a CYP2C9 and CYP3A substrate. The drug undergoes metabolism from N-acetylation and N-hydroxylation.
Elimination: Approximately 85% of the daily dosage of dapsone is recoverable in the urine as water-soluble metabolites. Dapsone and metabolites are formed in the liver as dapsone glucuronide, which is water-soluble and rapidly excreted via the kidneys.[7] Drug excretion is slow, and a steady serum level is maintained with indicated dosing.
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