Vasodilation caused winstrol for women when administered intravenously at doses used in order to visualize the myocardium, leading to regional redistribution of coronary blood flow, and, presumably due to “steal effect” may interfere with the distribution of thallium and ventricular function in patients with coronary heart disease.Normal blood vessels dilate to increase blood flow, while significantly stenotic coronary pressure and flow are reduced.
Dipyridamole inhibits phosphodiesterase in various tissues. The drug in dosage weakly inhibits cAMP-PDE activity, but inhibit cGMP PDE, thus increasing the concentration of cGMP produced by EDRF ( «relaxation factor released by the endothelium,” which is now identified as nitric oxide, N0).
Dipyridamole also stimulates the biosynthesis and release of prostacyclin by the endothelium.
Dipyridamole, increasing the concentration of the protective mediator 13-HODE (13-gidroksioktadekadienovaya acid), reduces thrombogenicity subendothelial structures.
(Most pharmacokinetic data obtained in healthy volunteers).
Adequate matching kinetics curves dipyridamole administered intravenously (60 mg / 75 min) obtained by using trehkompartmentnoy models:
a) rapid alpha phase with a half life of about 3 minutes. It presumably reflects distribution of the drug from the central compartment to the peripheral compartments,
b) a beta-phase half-life of about 40 minutes. It reflects removing most of intravenously administered drug and approximately 70% (together with alpha-phase) of the total value of AUC (i.e., is the dominant phase),
c) terminating the extended phase of the final clearance (Phase-gammaz) with a half-life of about 13 hours. It is about 30% of the total area under the curve “in the plasma concentration – time”, and probably corresponds to the central compartment Rediffusion small portion of the administered dose of remotely located fabrics having low capacitance. This phase may also reflect the presence of gepatoenteralnoy recycling (which manifests itself in the form of secondary peaks smaller, it is winstrol for women noted in a few hours after the infusion and appropriate meal times).
Apparent volume of distribution in the central compartment is about 5 l (similar to plasma volume). The apparent volume of distribution at steady state pharmacokinetics period is about 100 liters, which reflects the distribution of the drug in different compartments. The total clearance is about 200 ml / min and an average residence time of the body – of about 6.4 hours.
By the end of four-minute infusion at a dose of 0.5 mg / kg of dipyridamole mean concentration in the plasma was 6.30 ± 0.32 g / ml, and after 1 hour after – 1.13 ± 0.36 g / ml.
Distribution of dipyridamole
Due to the high lipophilicity of dipyridamole, log P 3,92 (n-octanol / 0, ln, NaOH), is distributed in many organs.
Animals dipyridamole is distributed mainly in the liver, then in the lungs, kidneys, spleen and heart.
The drug does not penetrate the blood-brain barrier. Penetration of the placenta dipyridamole is very low. A study conducted by one woman showed that dipyridamole concentration in breast milk was approximately 1/17 portion of the plasma concentration. dipyridamole protein binding is approximately 97 – 99%, and is carried out mainly with alpha 1-acid glycoprotein and albumin.
Metabolism of dipyridamole
Dipyridamole is metabolized in the liver by conjugation with glucuronic acid. This produces mainly monoglyukuronida and, in small quantities, diglucuronide.
After intravenous administration glucuronide concentrations are about 10% of the total formulation.
Elimination of dipyridamole
active substance in unchanged form excreted by the kidneys in small amounts. Glyukuronirovannyh excretion of metabolites in the urine is also low. Metabolites are mainly (about 95%) in the bile, and then with the feces. There is some gepatoenteralnaya recycling.
Pharmacokinetics in the elderly
Concentrations of winstrol for women drug in plasma in elderly patients in the case of oral administration were approximately 30-50% higher than in younger individuals. This difference is due mainly reduced clearance. After intravenous administration of the drug should expect a slow decline in plasma concentrations.
The pharmacokinetics in patients with impaired hepatic function
In patients with hepatic insufficiency changes dipyridamole concentrations were observed in plasma, but found an increase in the concentration of glucuronide (pharmacodynamically inactive metabolites). It is believed that in the absence of clinical signs of liver failure in dosing limitations dipyridamole required.
The pharmacokinetics in patients with impaired renal function
Since dipyridamole excretion by the kidneys are very few (5%), no pharmacokinetic changes are not expected in patients with renal insufficiency. In ESPS2 study in patients with creatinine clearance is from about 15 ml / min to> 100 ml / min, change indicators pharmacokinetics glyukuronirovannogo dipyridamole or its metabolite were noted (when correction data considering the age differences).
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