The maximum plasma concentration obtained after approximately winstrol only cycle.. The absolute bioavailability after oral nalmefene is 41%. Simultaneous treatment with diet high in fat increases total exposure , while the time to reach maximum blood concentration (Tmax) plasma increases to 30 minutes, which is not considered clinically significant.
Distribution of protein binding plasma is approximately 30%. The apparent volume of distribution of about 3200 liters. According to data obtained in the study of positron emission tomography (PET), after single and repeated administration of nalmefene in a daily dose 18.06 mg binding receptor 94-100% is achieved through 3 hours, suggesting that nalmefene readily crosses the blood-brain barrier. Biotransformation When administered nalmefene undergoes extensive metabolism to a major metabolite nalmefene-3-O-glucuronide mainly under the action of the isoenzyme and to a lesser extent by isoenzymes . Relatively small amounts of nalmefene to nornalmefena metabolized by the action of the isoenzyme and sulfonation. Nornalmefen in turn transformed into nornalmefen-3-O-glucuronide and winstrol only cycle. Metabolites not make significant contributions to the pharmacodynamic effects associated with exposure to the opioid receptors in humans, except which is comparable to the activity of nalmefene. However, the concentration is less than 10% of the concentration of nalmefene. For this reason, it is unlikely that active metabolite makes a significant contribution to the pharmacological effects of nalmefene. Excretion binding glucuronides is the primary mechanism determining nalmefene clearance. Renal excretion is the main route of excretion of nalmefene and its metabolites. 54% was excreted in the urine as winstrol only cycle and nalmefene itself as its other metabolites in urine are determined by an amount not exceeding 3% each. These data on the distribution, metabolism and excretion of nalmefene demonstrate its high hepatic clearance. Linearity / non-linearity The pharmacokinetics of nalmefene dozonezavisimy is linear in a dose range from 18.06 mg to 72.24 mg . In the equilibrium state compared to single dose of nalmefene observed an increase in and total drug exposure .
There were no significant differences in the pharmacokinetics of nalmefene, depending on gender, age or ethnicity. It was found that body size have limited impact on the pharmacokinetic parameters of nalmefene (with an increase in the size of the body clearance growing), but probably this difference is not clinically significant. Impaired renal function There is currently no pharmacokinetic data nalmefene orally in patients with renal insufficiency. Introduction of 1 mg of nalmefene intravenously to patients with severe renal failure resulted in an increase nalmefene exposure (dose-adjusted compared with healthy subjects. The half-life increased to 26 hours compared to healthy subjects.
Liver dysfunction When receiving a single dose of 18.06 mg of nalmefene in patients with mild to moderate hepatic impairment, an increase nalmefene exposure as compared to healthy subjects. In patients with mild hepatic impairment, an increase in the exposure of the drug is 1.5 times and reduced the clearance by approximately 35%. In patients with moderate hepatic impairment the exposure was increased by 2.9 times, the winstrol only cycle times and clearance was reduced by approximately 60%. Changes Tmax and T½ not have clinical significance in either group of patients. There is currently no data on the pharmacokinetics of nalmefene after oral administration in patients with severe hepatic impairment. Elderly patients Specific pharmacokinetic studies after oral administration of nalmefene in patients aged 65 years and older was conducted. In a study with intravenous administration of nalmefene no significant differences between age groups pharmacokinetics.
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