2010/06/14

DAPSONE

Pharmacological action

Protivoleproznoe means of sulfones. Has bacteriostatic action. The mechanism of action due to inhibition of synthesis of folic acid in parasites. It is active against a broad spectrum of microorganisms, but mainly against Mycobacterium leprae, and Plasmodium, Pneumocystis carinii.


Pharmacokinetics

Slowly absorbed from the gastrointestinal tract. Bioavailability - 70-80%. It is well distributed in the body, but particularly high concentrations are in liver, muscle, kidney and skin. The concentration in saliva - 18-27% of the concentration in the blood. Good crosses the placental barrier. T max - from 2 to 6 h. When used in single doses of 50 and 100 mg C max of 0.6-0.7 and 1.7-1.9 mg / ml, respectively.

Metabolised in the liver with the acetyltransferase with the formation of metabolite - monoatsetildapsona, which may be subjected to deacetylation and move back to dapsone. The equilibrium between them is created in a few hours. The rate of acetylation depends on how atsetilyatorom a patient - "fast" or "slow", while the rate of acetylation of the clinical effectiveness of therapy is not defined. Another way of its metabolism - a hydroxylation in the liver to dapsongidroksilamina. Linking dapsone plasma protein - 70-90%, and monoatsetildapsona - more than 90%.

T 1 / 2 to dapsone and monoatsetildapsona - 10-50 hours (average 30 h). 70-85% is slowly excreted by the kidneys in the form of dapsone and its metabolites (5-15% dapsone is obtained by active tubular secretion), the remainder is excreted in the form of metabolites, which are partly conjugated with glucuronic and sulfuric acids. Enterohepatic circulation is essential for the maintenance of certain concentrations of the drug in the blood during prolonged therapy.


Statement

As part of combination therapy: treatment and prevention of all forms of leprosy, malaria prevention, treatment and prevention of pneumocystis pneumonia, toxoplasmosis prophylaxis, treatment of cutaneous leishmaniasis.


Dosage regimen

Dosage regimen individual. As part of combination therapy is used in doses of 50-100 mg / day or 1.2 mg / kg / day. If necessary, the maximum daily dose is 300 mg. Treatment of long-term.


Side effect

On the part of the hemopoietic system: possible hemolytic anemia, methemoglobinemia (when receiving a daily dose of more than 200 mg), agranulocytosis.

On the part of the digestive system: rarely - nausea, vomiting, hepatitis.

Dermatological reactions: skin rash, exfoliative dermatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome.

Other: headache.


Contraindications

Severe anemia, increased sensitivity to dapsone.


Application of pregnancy and breastfeeding

If necessary, use of dapsone during pregnancy should be related to the alleged benefit to the mother and the possible risk to the fetus.

Dapsone is excreted in breast milk. Therefore, if necessary, use during lactation should decide the issue of termination of breastfeeding.


Cautions

Precautions used dapsone in patients with deficiency of glucose-6-phosphate dehydrogenase, as in this patient at increased risk of hemolytic anemia.

In the period of treatment necessary to control the picture of peripheral blood.


Drug Interactions

When applied simultaneously with probenecid marked decrease in excretion of dapsone and increase its concentration in blood plasma.

Rifampicin increases the plasma clearance of dapsone.

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