Ritonavir
When ATH:
J05AE03
Pharmacological action
Antiviral agent. It has a selective affinity for the HIV protease ASPAR and therefore has little inhibitory effect on the proper protease man.
Enzymatic cleavage makes it impossible to activate the protease precursor protein and leads to the synthesis of immature HIV particles, unable to initiate further development of infection. Proteolysis of polypeptides stops the life cycle of HIV replication his C2-symmetric part of core HIV protease, It has high selective affinity to it and has a weak inhibitory effect on human proteases. It increases the number of CD4-cells in the blood and decreases the concentration of viral RNA. It leads to an increase in the total number of leukocytes, platelets and lymphocytes.
In in vitro studies show, ritonavir has a marked inhibitory effect on the replication of both laboratory, and clinical strains of HIV.
Ritonavir is almost completely metabolized in the liver.
Pharmacokinetics
Absorption - 60 – 80 %, time to maximum concentration 2 – 4 o'clock. The apparent volume of distribution - 0,41 l / kg and is equal to the volume of water in the body distribution. Bioavailability - 94 %. Metabolized by cytochrome P450 system to hydroxylated inactive metabolites with subsequent glucuronidation. The major isozymes, responsible for the metabolism, являются CYP2B6, CYP3A4, CYP3A5, CYP3A7. Ritonavir is an inhibitor of CYP2D6 and CYP3A3 isoenzymes, CYP3A5, CYP3A7. Smoking, weight, age, flooring, CYP2D6-phenotype does not affect the clearance of the drug. Half life (T1 / 2) children 2 – 14 years 1,5 times shorter, than in adults, at the same time the maximum concentration (Сmax) the same. Repeatedly receiving the same dose Cmin, area under the concentration - time and T1 / 2 are reduced. Displayed through the intestine (20 – 40 % in unchanged form).
Testimony
Treatment of infections, caused by HIV.
Dosage regimen
When administered to adults – by 600 mg 2 times / day. To reduce the side effect on the first day can be used for 300 mg 2 times / day, followed by a gradual increase in dose 100 mg to achieve the recommended dose.
In children it is recommended to use in combination with antiviral nucleoside analogs. The recommended dose is on 400 mg / m2 2 times / day. To reduce the side effects can begin receiving a dose 250 mg / m2, with a further increase every 2-3 of the day on 50 mg / m2 at reception until, until a dose is reached 400 mg / m2 2 times / day. Determination of the dose is recommended for children at a special table-nomogram.
Side effect
From the digestive system: often – anorexia, nausea, vomiting, diarrhea, dry mouth, ulcerative lesions of the oral mucosa, belching, flatulence, violations of liver function tests; increasing liver and digestive enzymes.
From the central and peripheral nervous system: often – fear, insomnia, paresthesia around the mouth and on the periphery, dizziness, drowsiness.
The respiratory system: possible laryngitis, cough, pharyngitis.
From the hematopoietic system: decrease in hemoglobin, decrease in hematocrit, reduction in the number of red blood cells, reduction in the number of white blood cells, reduction in the number of neutrophils, increase in the number of eosinophils.
Metabolism: increase in uric acid, hyperlipidemia, weight loss, decrease in potassium, increased triglycerides.
Dermatological reactions: skin rash, itch, increased perspiration.
Other: expansion of peripheral vascular, mialgii.
Contraindications
Hypersensitivity to ritonavir.
Concomitant use with amiodarone, astemizolom, itraconazole, ketoconazole, bepridil, cizapridom, bupropion, klozapynom, digidroergotaminom, ergotamine, enkainidom, flekainidom, meperidine, nimozidom, piroksikamom, propafenone, propoksyfenom, xinidinom, rifaʙutinom, terfenadine, sodium clorazepate, flurazepama, diazepamom, estazolamom, midazolamom, triazolamom, zolpidem, alprazolam.
Pregnancy and lactation
With caution and in cases of extreme need to use during pregnancy and lactation.
Cautions
To use caution in patients with liver disease.
During treatment should regularly monitor liver function in patients with previous liver enzyme elevations and hepatitis, as well as long-term treatment and elderly patients.
Patients with hemophilia A and B type in some cases the likelihood of bleeding (the appearance of skin bruising and joint).
Drug Interactions
Rifampin, rifabutin, and smoking reduce the effect of ritonavir.
In an application with ritonavir dose reduction is required of the following drugs (as a result of reducing the intensity of their metabolism): clarithromycin in patients with renal insufficiency, desipramine, saquinavir.
In an application with ritonavir should increase the dose of hormonal oral contraceptives, teofillina.
Ritonavir increases the mean AUC sildenafil in 11 time, clarithromycin and trimethoprim on 77% and 20% respectively; AUC rifabutin and its metabolite increases 4 and 35 times, respectively,.
Ritonavir reduces the mean AUC of zidovudine (26%), teofillina (45%), ethinyl estradiol (41%), sulfamethoxazole (20%); while these drugs have no significant effect on the pharmacokinetics of ritonavir.
