In hypertensive patients reduces blood pressure (BP) by combined blockade and a 1 -adrenoceptor. Lowering blood pressure is not accompanied by a simultaneous increase in total peripheral vascular resistance, which occurs when taking non-selective beta-blockers. Heart rate (HR) is somewhat reduced. Renal blood flow and renal function in patients with are stored. It is testosterone cypionate injection shown that does not change the stroke volume and decreases total peripheral vascular resistance; It does not disturb the blood supply to organs and peripheral blood, including in skeletal muscle, forearms, lower limbs , skin, brain and carotid artery. Cold extremities and fatigue during exercise are rare. Antihypertensive effect of when stored for a long time.
In patients with coronary heart disease, has anti-ischemic and anti-anginal action (increase in the total duration of exercise, time to ST depression depth of 1 mm and the time to occurrence of angina attack), the continuing long-term therapy. significantly decreases myocardial oxygen demand and activity simpatoadrenalovoj system. Preload also reduces the (wedge pressure in the pulmonary artery and pulmonary capillary pressure) and afterload (total peripheral vascular resistance).
Chronic heart failure
reduced mortality and reduced hospitalization rates, reduces symptoms and improves left ventricular function in patients with chronic heart failure of ischemic and non-ischemic origin. effects are dose-dependent.
After oral is rapidly absorbed . is a substrate-transporter protein that performs the role of the pump in the intestinal lumen, R. Glycoprotein P glycoprotein played a major role in the bioavailability of certain drugs. The maximum plasma concentration (C max ) reached after about 1 hour. The absolute bioavailability testosterone cypionate injection of is approximately 25%.
has high lipophilicity. Approximately 98-99% of is bound to plasma proteins. Its volume of distribution of about 2 liters / kg.
is biotransformation in the liver by oxidation and conjugation with the formation of a number of metabolites. 60-75% of the absorbed drug is metabolized at a “first pass” through the liver. The existence of enterohepatic circulation of the starting material.
Metabolism by oxidation of is stereoselective. R stereoisomer metabolized mainly by CYP2D6 and CYP1A2, and S stereoisomer – mostly via CYP2D9 and to a lesser extent via CYP2D6. Other isoenzymes the P450, involved in the metabolism of include CYP3A4, CYP2E1 and CYP2C19. R stereoisomer maximum concentration in plasma is approximately 2 times greater than that for the S stereoisomer.
R stereoisomer is metabolized mainly by hydroxylation. At slow metabolizers CYP2D6 may increase the plasma concentration of , especially, R stereoisomer, resulting in increase in alpha activity adrenoblokiruyuschey .
Demethylation and hydroxylation of the phenolic ring 3 formed metabolite (concentrations 10 times lower than the concentration of the starting material) with the beta-adrenoblokiruyuschey activity (4′-hydroxyphenol in the metabolite is about 13 times stronger than that of ). 3 active metabolite exhibit less pronounced vasodilating properties than . 2 of gidroksikarbazolnyh metabolites of are extremely potent antioxidants, and their activity in this respect 30-80 times greater than at .
The half-life of is about 6 hours and plasma clearance – about 500-700 ml / min. Excretion occurs mainly through the intestine , the main excretion pathway – with bile. A small part of the dose is excreted by the kidneys in the form of various metabolites.
Pharmacokinetics in special patient groups
Patients with impaired renal function
Prolonged therapy intensity of renal blood flow is maintained, the glomerular filtration rate does not change.
In patients with and a violation under the curve “concentration-time” renal function area (AUC), half-life and maximum plasma concentration does not change. Renal excretion of unchanged drug in patients with renal insufficiency is reduced, testosterone cypionate injection however, pharmacokinetic parameters change with the slightly pronounced.
is an effective treatment for patients with renovascular , including patients with chronic renal insufficiency and in patients undergoing hemodialysis or kidney transplant. causes a gradual reduction in blood pressure of dialysis day, and on days without dialysis, with its hypotensive effect comparable to that of patients with normal renal function. During dialysis is output, since it does not pass through the dialysis membrane, probably because the strongly bound to plasma proteins.
Based on the results obtained in comparative studies of patients undergoing hemodialysis, it is concluded that the is more effective with a better tolerability in comparison with blockers “slow” calcium channels.
Patients with hepatic impairment
In patients with liver cirrhosis systemic bioavailability is increased by 80% due to reduced expression of metabolism in the “first pass” through the liver. Therefore, is contraindicated in patients with symptomatic hepatic impairment (see. “Contraindications”).
Patients with heart failure
In a study of 24 patients suffering from heart failure, the clearance R and S stereoisomers of was significantly lower compared to the previously observed clearance in healthy volunteers. These results indicate that the pharmacokinetics of R and S stereoisomers heart failure varies considerably.
Age has no statistically significant effect on the pharmacokinetics of in hypertensive patients. According to clinical trials, tolerability of in patients with or coronary artery disease in elderly heart does not differ from that of younger patients.
Data on the pharmacokinetics in patients under 18 years are currently limited.
In patients with type 2 diabetes and , does not affect the concentration of glucose in blood on an empty stomach and after a meal, the level of glycosylated hemoglobin (HbA 1 ), or a dose of hypoglycemic agents for oral administration . It was shown in some clinical studies that in patients with diabetes 2 type not cause a decrease in glucose tolerance. In patients with who had insulin resistance (syndrome X), but without concomitant diabetes mellitus , improves insulin sensitivity. Similar results were obtained in patients with and Type 2 diabetes. astralean