Analysis of dianabol pills isolated from biopsy specimens of skin lesions of psoriasis at baseline and after 2 weeks of treatment showed that the use Ctelara preparation ® resulted in gene expression reducing encoding its molecular target , as well as genes encoding inflammatory cytokines and chemokines – monocyte chemotactic factor , tumor necrosis factor, interferon-gamma – inducible protein . These data are consistent with a significant clinical benefit of treatment in patients with psoriasis.
The clinical effect of treatment of psoriasis and psoriatic arthritis, apparently depends ustekinumab concentration in blood plasma. Patients with psoriasis with the best result evaluation scale area and severity of psoriasisustekinumab mean value of concentration in plasma was higher than that of patients with less clinical effect. In general, the proportion of patients with improvement in scale reached 75%, increased with increasing concentrations of ustekinumab in the blood plasma. In patients with psoriatic arthritis who have reached assessment, there is a higher average concentration of ustekinumab in plasma compared with patients not responding to treatment. The number of patients with psoriatic arthritis, the scale improvement by , increased with increasing ustekinumab concentration in blood plasma.
In the long phase 3 clinical study in patients receiving the drug dianabol pills at least developed an immune response 3.5 years, similar to those of the control group of patients with psoriasis, but not undergoing systemic treatment when administered vaccines comprising a pneumococcal polysaccharide or tetanus vaccine.
At about the same amount (%) of patients receiving treatment , and patients in the control group achieved protective concentration protivopnevmokokkovyh and tetanus antibodies. Antibody titers were about the same.
The mean time to maximum plasma concentration (Tmax) after a single subcutaneous injection of 90 mg of ustekinumab in healthy volunteers was 8.5 days. At this value psoriasis drug at doses of 45 or 90 mg was comparable to that in healthy volunteers. The absolute bioavailability of ustekinumab following a single subcutaneous administration to patients with psoriasis was 57.2%.
Average value of volume distribution ustekinumab in the terminal phase elimination after single intravenous psoriasis patients ranged from 57 to 83 ml / kg.
The metabolic pathway ustekinumab is unknown.
The mean value of systemic clearance ustekinumab following a single intravenous administration to patients with psoriasis ranged from 1.99 to 2.34 ml / day / kg. The average half-life (T 1/2 ) ustekinumab in patients with psoriasis and / or psoriatic arthritis was approximately 3 weeks, and in different studies ranged from 15 to 32 days.
Systemic exposure ustekinumab in patients with psoriasis introduced proportionally increased after single dose intravenous doses ranging from 0.09 mg / kg to 4.5 mg / kg, and also after a single subcutaneous injection of doses ranging from 24 mg to 240 mg.
Changing ustekinumab concentrations in blood plasma over time after single or repeated injections of multiple drug was generally predictable. The equilibrium concentration of ustekinumab achieved by week 28 in blood plasma in the proposed therapy mode (second injection 4 weeks after the first use, then every 12 weeks). On average, the equilibrium concentration of the drug in patients with psoriasis is 0,21-0,26 mg / ml for a dose of 45 mg and 0,47-0,49 mg / ml for a dose of 90 mg. Accumulation of the drug in the serum was not observed during the treatment with a dosage regimen 1 injection every 12 weeks.
Effect of patient body weight on the pharmacokinetics of the drug
concentration in blood plasma drug depends on the weight of the patient with psoriasis and / or psoriatic arthritis. When administered the same dose (45 mg or 90 mg), patients weighing over 100 kg ustekinumab mean concentration in the plasma was less than in patients weighing less than 100 kg. However, the mean minimum plasma concentration ustekinumab patients weighing more than 100 kg, which was administered 90 mg dose was comparable to that in patients weighing less than 100 kg, which was administered 45 mg.
It was analyzed the influence of comorbid conditions (diabetes, hypertension, hyperlipidemia) on the pharmacokinetics of the drug in patients with psoriasis. In patients with diabetes dianabol pills value was an average of 29% higher than in healthy patients.
Population pharmacokinetic analysis showed that there is a tendency of increasing ustekinumab clearance in patients with a positive immune response. deca 300