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proviron libido

After oral administration of the drug to patients with liver transplant patients most equilibrium concentration achieved within 3 days.
Patients with liver transplant in a stable state decreased bioavailability with oral medication postprandial moderate fat diet. It was also observed decrease the area under the concentration-time curve AUC (27%), maximum concentration C max (50%) and an increase in t max (173%) in the whole blood. With the simultaneous application of the drug with food decreased the rate and extent of absorption .
Isolation of bile does not affect the absorption
There is a strong correlation between theproviron libido and minimum levels of the drug in whole blood upon reaching equilibrium, therefore minimal monitoring drug levels in whole blood can be used to adequately assess the systemic exposure of the drug.

Distribution The distribution of tacrolimus after intravenous administration of the drug the person has a biphasic pattern. in systemic circulation tacrolimus is largely associated with red blood cells. The distribution ratio of whole blood plasma concentration is approximately 20: 1. The blood plasma drug largely associated (> 98.8%) with the proteins, mainly serum albumin and α-1-acid glycoprotein. Tacrolimus is widely distributed in the body. The equilibrium volume of distribution based on plasma concentrations is approximately 1300 l (healthy volunteers). The corresponding figure from whole blood, the average is 47.6 liters. Tacrolimus is a drug with low clearance. In healthy volunteers, the mean value of the total clearance, as measured by the concentrations of drug in whole blood was 2.25 l / h.

In adult patients proviron libido with kidney and liver transplants this value was 4.1 liters / hour and 6.7 liter / hour, respectively. Children with liver transplant total clearance value of approximately 2-fold higher than in adult patients with liver transplant. The half-life of tacrolimus is long and variable. In healthy volunteers, the mean value of the half-life of whole blood is about 43 hours. In adult and pediatric patients with hepatic graft half-life averages 11.7 hours and 12.4 hours, respectively, compared to 15.6 hours in adult kidney transplant patients. Metabolism When using in vitro models identified metabolites 8 among which only one metabolite has significant immunosuppressive activity. tacrolimus is largely metabolized by hepatic microsomal cytochrome  isoenzymes.

Excretion Following intravenous and oral administration of tacrolimus, labeled with 14 C isotope, the majority of the radioactively-labeled drug is excreted in the faeces. Approximately 2% is excreted in the urine. Less than 1% of unchanged tacrolimus was detected in the feces and urine, indicating that tacrolimus almost completely metabolized to elimination. The main route of elimination is the bile.

 

Indications

Prevention and treatment of allograft rejection liver, kidney and heart, including refractory to standard immunosuppressive regimes.

Contraindications

Known hypersensitivity to tacrolimus or other macrolides.
Known hypersensitivity to polyoxyethylated hydrogenated castor oil (HCO-60) or structurally related components.

Dosing and Administration

Can be applied both orally and intravenously. If required, the capsule contents can be dissolved in water and administered through a nasogastric tube.
The dosage should be adjusted  depending on the individual patient’s needs, taking into account the results of monitoring drug levels in the patient’s blood.

It is recommended to divide the daily oral dose of two doses (for example, morning and evening). The capsules should be taken immediately following removal from the blister packaging. You need to swallow capsules, drinking liquid (preferably water).
To achieve maximum absorption of the capsules to be taken on an empty stomach (fasting) or, at a minimum, for 1 hour or 3.2 hours after ingestion.
There was no significant effect of food on the absorption of the drug in patients with kidney transplant.

 Concentrate for solution for infusion of 5 mg / ml.
The concentrate for intravenous infusion should only be used after diluting it with an appropriate solvent.
Infusion concentrate comprising 5 mg / ml, should not be injected undiluted.
Concentrate for infusion containing 5 mg / mL should be diluted with 5% dextrose solution, or physiological saline solution in glass, polyethylene or polypropylene bottles. Only clear and colorless solution should be used.
It is not recommended bolus formulation.
Concentration of the solution for infusion should vary within 0,004-0,100 mg / ml total volume of infusion for 24 hours should vary between 20-500 ml.
Unused concentrate for infusion in an open vial or unused reconstituted solution should be immediately thrown away in order to avoid its pollution (contamination).

Recommended dosage

proviron libido – adult oral therapy  must begin with dosages 0 10 – 0 20 mg / kg / day, dividing the dose into two doses (eg morning and evening). Use of the drug should be started about 12 hours after the operation is complete. If the patient’s condition does not allow to take the drug inside, intravenous therapy must begin with a dosage of 0.01 – 0.05 mg / kg / day by injecting medicine as an intravenous infusion over 24 hours. Initial immunosuppression – Children Initial dose oral 0 30 mg / kg / day should be divided into two stages (for example, morning and evening). If the clinical condition of the patient does not allow him to take medication by mouth, should begin therapy with intravenous dosing of 0.05 mg / kg / day by intravenous infusion for 24 hours.Maintenance therapy – adults and children during maintenance therapy dosage is usually lowered. In some cases it is possible to cancel the drugs concomitant immunosuppressive therapy, leaving as the base alone. Improved patient after transplantation can alter the pharmacokinetics of tacrolimus and the need arises to correct dose. To achieve similar blood levels of the drug to children usually require dosages of 1.5 – 2 times higher than the doses for adults. Rejection Treatment – adults and children. For treatment of rejection episodes is necessary to use higher doses of  combined with additional corticosteroid therapy, and introduction of short courses of mono- / polyclonal antibodies. If signs of toxicity may require dose reduction .

 

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