Zidovudine is a thymidine analogue and belongs to the group of nucleoside antiviral drugs. It has strong inhibitory activity against retroviruses, including human immunodeficiency virus .
The infected human cells is phosphorylated by the action of thymidine kinase to azidothymidine triphosphate, which is a substrate inhibitor of reverse transcriptase of retroviruses: the introduction of azidothymidine triphosphate in the synthesized circuit virus , its further formation blocked virus reproduction stops, on which is based the therapeutic effect to reduce concentrations the patient’s blood. Azidothymidine triphosphate Competitive inhibitory activity against reverse transcriptase is approximately 100 times greater than that observed for the polymerase alpha of human cells, thus clenbuterol dosage has no effect on the normal metabolism of the human body.
It was found that low concentrations of zidovudine inhibit many strains of Enterobacteriaceae in vitro, including strains of various species coli (bacteria with resistance develops quickly). Activity against Pseudomonas aeruginosa in vitro has not been established. In very high concentrations (1.9 mcg / ml (7 mmol / L)) suppresses Giardia lamblia, although activity against other protozoa absent.
Clenbuterol dosage is well absorbed from the gastrointestinal tract, maximum concentration (Cmax) in blood is achieved in 30-90 minutes, the bioavailability is 63%. It penetrates the blood-brain barrier (BBB) and is found in the cerebrospinal fluid ( in a concentration of 15-64% of the initial dose.
It penetrates through the placenta, so that its concentration in cord blood is comparable to that in maternal blood. It is found in breast milk. Metabolism occurs in the liver to form a glucuronide which is excreted from the body by the kidneys in the urine.
In patients with impaired hepatic function possible cumulation of zidovudine by decreasing glyukuronirovaniya in the liver.
Data on the pharmacokinetics of zidovudine in pregnant women is limited, as well as in older patients. Children over the age of 5-6 months. Zidovudine pharmacokinetic data are similar to those in adults.
Reception with fatty food reduces the rate and extent of absorption.
When inside designation 200 mg six times daily plasma, the minimum concentration (Cmin) – 0,1 mcg / ml of plasma. It penetrates through the BBB, the concentration in CSF – 24% of the plasma concentration in children. It passes through the placenta (concentration in the tissues of the central nervous system in 13-week fetal – 0.01 mmol / l, which is below the effective antiviral concentration). The volume of distribution clenbuterol before and after in adults and children – 1.4-1.7 l / kg (42-52 l / m). It accumulates in the seminal fluid, wherein the concentration exceed those in serum 1,3-20,4 times, but does not affect the elimination of HIV from semen and therefore can not prevent the sexual transmission.
The average half-life (T?) Of cells – 3.3 hours; serum from adults – about 1 h (0.8-1.2 h), renal failure (creatinine clearance (CC) of less than 30 ml / min) – 1.4-2.9 hours at cirrhosis – varies depending on the severity of liver disease, on average, 2.4 hours; in children aged 2 weeks-13 years – 1-1.8 hours in neonates (whose mothers received zidovudine) -13 hours Renal clearance -. 27.1 mL / min / kg in children – 30.9 ml / min / kg, exceeds KK. In the liver occurs conjugation with glucuronic acid; primary inactive metabolite – 3′-azido-3′-deoxy-5′-O-beta-D-glyukopiranurono-ziltimidin, T? normal kidney function h -1, renal insufficiency – 8 hours at anuria – 29-94 h at cirrhosis – varies depending on the extent of liver failure, on average, about 2.4 hours; excreted by the kidneys and does not exhibit antiviral activity.
In unchanged form excreted by the kidneys by 14-18% in children – 30%; in the form of glucuronides – 60-74% in children – 45%. Not accumulates; in patients with chronic liver failure may be the accumulation of metabolites (conjugates with glucuronic acid), which increases the risk of symptoms of toxic action.
Indications for use in adults and children over 2 years of HIV infection at the stage of secondary diseases in the stage of acute infection and the primary clinical manifestations at lower less , as well as in the incubation stage.
Pregnant women may be administered with the progression of secondary diseases in HIV infection or when the number of clenbuterol dosage lymphocytes is less than 0.2 x 109%. In other cases, treatment zidovudine can be interrupted before cytomel uk the expiry of the first trimester of pregnancy.
Perenatalnoy Prevention of HIV transmission from an infected mother to child, as zidovudine reduces the risk of intrauterine infection.
Preventing contamination of persons who have received injections and cuts while work with HIV-contaminated material.
Contraindications – Hypersensitivity to the drug; – leukopenia (neutrophil count less than 500 l) – anemia (hemoglobin (Hb) less than 50 g / l); – thrombocytopenia (platelets less than 25 thousand in l.); – Improving aminotransferases and creatinine than 3 times the upper limit of normal; – children under 2 years old.
Precautions: inhibition of bone marrow hematopoiesis, deficiency of cyanocobalamin (vitamin B12) and folic acid, liver failure, older age, obesity, with hepatomegaly, hepatitis or any known risk factors for liver disease. In the treatment of zidovudine such patients should be carefully monitored.