Suction
When administered orally, the maximum bioavailability of itraconazole is noted when taking capsules immediately after meals. The time to reach the maximum concentration in the blood plasma is 3-4 hours.
Distribution
The equilibrium concentration of itraconazole in the plasma 3-4 hours after taking the drug is 0.4 μg / ml (with 100 mg once a day), 1.1 μg / ml (with 200 mg one dose per day) and 2, 0 μg / ml (with taking 200 mg twice a day).At long reception the equilibrium concentration is reached within 1-2 weeks. Connection with plasma proteins - 99,8%.
Itraconazole penetrates well and is distributed in tissues and organs. The concentration of the drug in the lungs, kidneys, liver, spleen, stomach, bones, skeletal muscles is 2-3 times higher than its concentration in the plasma.
Accumulation of itraconazole in keratin tissues, especially in the skin, is 4 times higher than in plasma, and the rate of excretion depends on the regeneration of the epidermis.
In contrast to plasma concentrations that are not detectable within 7 days after cessation of treatment, the therapeutic concentration of itraconazole in the skin persists for 2-4 weeks after the cessation of the 4-week course of treatment; in the mucous membrane of the vagina - within 2 days after the end of the 3-day course of treatment at a dose of 200 mg per day and 3 days after the end of a one-day course of treatment at a dose of 200 mg twice a day. The therapeutic concentration of the drug in the nail keratin is determined 1 week after the start of treatment and is maintained for 6 months after the completion of the 3-month course of therapy. Itraconazole is also determined in the secretion of the sebaceous and sweat glands.
Metabolism
Metabolized by the liver with the formation of active metabolites, one of which - hydroxyitraconazole - has an antifungal action comparable to itraconazole in vitro.
Excretion
Excretion from the plasma is biphasic with a finite half-life of 24-36 hours. Excretion with feces is from 3 to 18% of the dose. Kidney excretion - less than 0,03% of the dose. Approximately 35% of the dose is excreted as metabolites in urine for 1 week.
Pharmacokinetics in special clinical cases
In patients with renal insufficiency, as well as in some patients with impaired immunity (eg, in AIDS, after organ transplantation or in case of neutropenia), the bioavailability of itraconazole may decrease.
In patients with cirrhosis of the liver, the bioavailability of itraconazole is reduced, the half-life is increased.