Rotigotine is neergolinovym agonist D1-3 dopamine receptors (ADRs), used to treat Parkinson’s anadrol cycle disease. The therapeutic effect of rotigotine is caused by activation of D3, D2, and D1 receptors kaudato-putamenalnogo (basal ganglia – the caudate and putamen) brain complex. Rotigotine attenuates the severity of the clinical manifestations of idiopathic Parkinson’s disease (UPS).
The efficacy of rotigotine in the treatment of patients UPS confirmed by the results of 4 randomized, double-blind, placebo-controlled studies.
In 2 studies, the drug was administered to patients without concomitant dopamine receptor agonist therapy who did not receive medication levodopa or received them no more than 6 months. As the main criterion for evaluating the effectiveness of therapy used for the amount of points II (daily activities) and III (motor activity), part of the “Unified Parkinson’s disease assessment scale” (USHOBP). In both studies, the initial dose of rotigotine was 2 mg / 24 h. Her weekly increased by 2 mg / 24 h until reaching the optimal dose which was maintained for 6 months.
In the first double-blind study, 177 patients received rotigotine and 96 patients received placebo. At the end of treatment was the optimal dose of 6 mg / 24 h in 91% of patients it coincides with a maximum permissible dose.
Improvement of 20% was observed in 48% of patients in group rotigotine and 19% – in the placebo group, the advantage of rotigotine was 29% (p <0.0001). Improving on USHOBP in the rotigotine group was 3.98 points (total score before treatment – 29,9), while the placebo group showed a deterioration of 1.31 points (total score before treatment – 30,0). The difference between placebo and rotigotine was 5.28 points and statistically significant (p <0.0001).
In the second double-blind study, 213 patients received rotigotine, 227 patients received ropinirole and 117 patients received placebo. Patients taking rotigotine, to select the optimal dose for 4 weeks, starting with 2 mg / 24 h to a maximum dose of 8 mg / 24 h. Patients taking ropinirole, the maximum dose was reached within 13 weeks, and was 8 mg / 24 hours. Patients were on optimal dose for 6 months. At the end of treatment in the group of rotigotine optimum dose coincided with the maximum permitted dose of 8 mg / 24 hours in 92% of patients.
In 2 other studies, rotigotine was administered to patients receiving concomitant therapy with levodopa. Rotigotine initial dose of 4 mg / 24 h weekly increased by 2 mg / 24 h to achieve the optimal dose. The primary efficacy criterion was used duration of “off” time (hours).
In the first of these double-blind studies comparing the effectiveness of rotigotine 8mg / 24 h (113 patients) and 12 mg / 24 h (109 patients) and placebo (119 patients). Patients were on optimal dose for 6 months. At the end of treatment 30% improvement was observed in 57% of patients and 55% respectively in patients receiving 8 mg and 12 mg rotigotine per day, and in 34% of patients in the placebo group. The average decrease in the duration of “off” period during treatment with rotigotine was, respectively, 2.7 hours and 2.1 hours in the placebo group -. 0.9 hours (the differences were statistically significant).
In the second double-blind study, 201 patients received rotigotine, 200 patients received pramipexole and 200 patients received placebo.
In the group of rotigotine starting dose is 4 mg / 24 h and increased to a maximum dose of 16 mg / 24h.
The average anadrol cycle reduction in the length of time “off” during treatment with rotigotine was 2.5 hours, with pramipexole – 2.8 hours, placebo – 0.9 hours (all differences between the study drug and placebo were statistically significant).
After sticking plaster transdermal (PT) rotigotine is continuously released and absorbed through the skin. The equilibrium concentrations of rotigotine are achieved within 1-2 days after application of the PT and maintained for 24 hours in the same range of values for a single daily application of FET. Dose proportional increase in the plasma concentration of rotigotine in the range from 1 mg / day to 24 mg / day.
Approximately 45% released from rotigotine FET 24 h. The absolute bioavailability of rotigotine transdermal application is about 37%.
Alternating sections of the PT application may be accompanied by daily fluctuations of rotigotine plasma concentrations. Differences in bioavailability of rotigotine are between 2% (between the shoulder and the side surface of the body) to 46% (between the girdle and the thigh). However, the clinical significance of this has not.
Binding proteins rotigotine in vitro blood plasma is about 92%. The apparent volume of distribution is approximately 84 l / kg.
The body rotigotine undergoes extensive metabolism, primarily by N-dealkylation as well as direct and indirect conjugation. In vitro research data shows that to catalyze the N-dealkylation of rotigotine capable of various cytochrome P450 isozymes. The main metabolites are biologically inactive.
Approximately 71% of the active substance rotigotine eliminated via the kidneys, a smaller part (about 23%) is excreted in the feces.
Clearance Rotigotine transdermal application at about 10 l / min and the half-life -. 7.5 h excretion is biphasic with an initial half-life of 2-3 hours.
Because of rotigotine PT absorbed through the skin, the effect of food intake and of the gastrointestinal tract to the clinical characteristics of rotigotine unlikely
Pharmacokinetics in specific patient groups
In patients with moderate hepatic insufficiency and renal failure of varying severity is not a significant increase in rotigotine plasma concentrations was observed.
If the kidney function in blood plasma increases the concentration of metabolites of rotigotine, anadrol cycle but the clinical significance of this phenomenon is not known.
In patients with severe hepatic impairment has not been studied rotigotan.
Monotherapy (without co-use with levodopa) early stages of idiopathic Parkinson’s disease or in combination with levodopa (as the disease progresses), including the late stages, in which the therapeutic effect of levodopa becomes unstable and there are motor fluctuations (the phenomenon of “exhaustion” a single dose of levodopa, the phenomenon of “on-off”).
- Hypersensitivity to rotigotine and / or other ingredients, including sulfites
- Children under the age of 18 years (no data on the safety and efficacy)
Conducting of magnetic resonance imaging or cardioversion during treatment with the drug is contraindicated (see. “Special Instructions”).
It should be used with caution in rotigotan patients taking sedative drugs, benzodiazepines, antidepressants consume alcohol (in connection with a possible mutual reinforcement effect), as well as patients with severe hepatic insufficiency (due to the possibility of reducing the clearance of rotigotine).
Application of pregnancy and during breastfeeding
Controlled studies of rotigotine in pregnant women were not conducted. Preclinical studies revealed no evidence of teratogenic activity of the drug, however, the specific dose provided fetotoxic effect. The potential risk of embryotoxic effect for humans is unknown. The drug Nyupro ® should not be used during pregnancy.
The period of breastfeeding
Rotigotan reduces the secretion of prolactin and decreases the amount of breast milk. According to preclinical studies, rotigotan and / or its metabolites are excreted in breast milk. Due to the lack of data on rotigotine excretion in breast milk in humans, breast-feeding should be discontinued.
Women of childbearing age
Women of child-bearing function with preserved against the background of treatment with must use adequate contraception to prevent pregnancy.
Effect of Rotigotine on reproduction was investigated in rats, rabbits and mice. Rotigotine teratogenic effect was detected in all three species, but embryotoxicity was observed in rats and mice at doses that are toxic to pregnant females.
Rotigotine no effect on anadrol cycle the fertility of male animals in mice, but distinctly reduced fertility in female individuals in rats and mice by influencing prolactin, which plays an important role in rodents. If you want buy steriod cycles online