Thus, even if the concentration of abacavir metribolone methyltrienolone dosageat 4 hours after administration at a dose of 600 mg two times a day and does not reach the maximum, it exceeds , about 9 times. Metabolism since only a small portion of lamivudine is metabolized in the liver (5-10%), and also because of a slight binding to plasma proteins, metabolic interactions of lamivudine with other drugs are unlikely. Lamivudine is excreted unchanged by renal excretion. Zidovudine is primarily metabolized in the liver.
The major metabolite of zidovudine in plasma and urine is a 5-glucuronide of zidovudine, which is excreted by the kidneys and is about 50-80% of the dose of the drug. Other metabolites of when administered parenterally is 3′-amino-3′-deoxythymidine. Abacavir is primarily metabolized in the liver, only 2% of the dose is excreted unchanged by the kidneys. In humans, abacavir metabolized mainly by the action of alcohol dehydrogenase with the formation of carboxylic acids and 5′- by conjugation with glucuronic acid to form a 5′-glucuronide, which constitute about 66% of the total administered dose. Elimination lamivudine is 5-7 hours.
More than 70% of lamivudine excreted by the kidneys with the participation of the transport system of organic cations, the total clearance is an average . According to research on / in the introduction of zidovudine, averages 1.1 hours and the average total clearance . Renal clearance, which indicates the active glomerular filtration and tubular secretion of zidovudine. In patients with severe renal impairment zidovudine plasma concentration increased. The average value of the T 1/2 of abacavir is about 1.5 hours. Long-term use of abacavir 300 mg orally 2 times does not lead to significant accumulation of abacavir in the day. Abacavir is metabolized in the liver and its metabolites are excreted mainly in urine. About 83% of the drug in the form of metabolites and unchanged in the kidneys, the remaining amount.
Specific patient groups Elderly The metribolone methyltrienolone dosage of the drug in patients older than 65 years have not been studied. Patients with renal impairment In a study of patients with impaired renal function has been shown, that the elimination of lamivudine slows down due to the reduction in renal clearance. If creatinine clearance less than 50 mL / min, an adequate correction of dosing regimen. Increasing zidovudine plasma concentrations is observed only in patients with severe renal dysfunction. Since less than 2% of abacavir excreted by the kidneys in unchanged form, its pharmacokinetics in patients with end-stage renal failure patients differs from that in patients with normal renal function. since patients with reduced renal function (creatinine clearance below 50 ml / min) may require dose reduction of lamivudine and zidovudine, it is recommended to appoint monocomponent drugs lamivudine, zidovudine and abacavir. patients with hepatic impairment The few data obtained in patients with impaired hepatic function, suggest a possible accumulation of zidovudine in connection with a reduction in the formation of glucuronide speed. In studies in patients with impaired liver function moderate and severe There were no significant changes in the pharmacokinetics of lamivudine. The study pharmacokinetics of abacavir in patients with mild impairment of liver function. On theof metabolites of abacavir decrease in liver function is not affected, but the rate of their formation and excretion is reduced. Therefore abacavir dose should be reduced in patients with impaired liver function mild. The pharmacokinetics of abacavir in patients with impaired liver function moderate and severe has not been studied.
Clinical efficacy in metribolone methyltrienolone dosage patients who have not previously received antiretroviral treatment, the combination of abacavir, lamivudine and zidovudine causes a steady decline in viral load at 48 weeks than the combination of lamivudine with zidovudine. In a similar group of patients in about 70% of them virologic response was maintained over 120 weeks. The use of a combination of lamivudine, abacavir and zidovudine in combination with efavirenz in patients who have not previously received antiretroviral treatment for 24 weeks resulted in a reduction in viral load to 400 copies / ml in about 90% of them, with 80% of patients with a viral load less than 50 copies / mL. data analysis of a randomized double-blind clinical trial of abacavir combination with lamivudine and zidovudine, and indinavir, lamivudine and zidovudine, used in the course of 48 weeks, adult HIV-infected patients who have not received antiretroviral therapy has shown comparable antiviral effects of these combinations.However, in a subgroup of patients with baseline HIV-1 RNA in blood plasma, greater than 100,000 copies / mL, the combination comprising indinavir, was more effective. At baseline, less than 100 000 copies / mL effectiveness of both combinations of the same. In an ongoing clinical trial of abacavir-lamivudine-zidovudine and nelfinavir-lamivudine-zidovudine patients who have not previously received antiretroviral treatment, it was found that during the first 16 weeks of treatment efficacy compared combinations of the same. In patients with baseline low viral load (less than 5,000 copies / ml), and the average length of antiviral therapy, addition of abacavir to have used a combination of lamivudine with zidovudine, was characterized by a moderate decrease in viral load to 48 weeks of therapy. currently, there is no data on the use patients, with many years of antiretroviral therapy in patients who are not responding to treatment, A. The effectiveness patients previously treated with highly active antiretroviral therapy , it depends on the type and duration of prior therapy that could lead to the development of strains of metribolone methyltrienolone dosagecross-resistance to abacavir, lamivudine or zidovudine. efficacy and safety data applications in combination with non-nucleoside reverse transcriptase inhibitors or protease inhibitors are currently not sufficient.
of HIV infection in adults and children over 12 years as an anti-retroviral therapy.
- Hypersensitivity to abacavir, lamivudine or zidovudine, or any other component of the tablet formulation;
- Abnormal liver function;
- Marked reduction in the number of neutrophils (less than 0.75 x 10 9 / L) or hemoglobin level (less than 7.5 g / dl or 4.65 mmol / l).
- End-stage renal disease