Grandazole® [Levofloxacin, Ornidazole]

Pharmacological properties

the pharmacological effect of levofloxacin is antibacterial (bactericidal). inhibits dna gyrase (topoisomerases ii and iv), disrupts the process of supercoiling and crosslinking of DNA breaks, inhibits cell division, causes structural changes in the cytoplasm and death of microorganisms.

It has a wide spectrum of action. It mainly affects gram-negative and some gram-positive microorganisms: Citrobacter diversus, Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Citrobacter diversus, Neisseria gonorrhoeae, Chlamydia trachomatococomusocaphylus, Staphomatus, Staphomatus, Staphomatus, Staphomatus, Staphomatus. Effective against microorganisms that are resistant to most antibiotics and sulfa drugs.

The pharmacological effect of ornidazole is antibacterial and antiprotozoal. It is active against Trichomonas vaginalis, Entamoeba histolytica, and Giardia lamblia (Giardia intestinalis), as well as some anaerobic bacteria (Clostridium spp., Bacteroides spp., Fusobacterium) and anaerobic cocci. According to the mechanism of action, ornidazole is a DNA tropic drug with selective activity against microorganisms having enzyme systems capable of reducing the nitro group and catalyzing the interaction of proteins of the ferridoxin group with nitro compounds. After the drug penetrates into the cell of the microorganism, its mechanism of action is due to the restoration of the nitro group under the influence of nitroreductases of the microorganism and the activity of the already reduced nitroimidazole. Recovery products form complexes with DNA, causing its degradation, disrupt DNA replication and transcription. In addition, the metabolic products of the drug have a cytotoxic property and disrupt the processes of cellular respiration.

Pharmacokinetics

Levofloxacin

Absorption. When taken orally, levofloxacin is rapidly and almost completely absorbed, while_max in blood plasma is achieved within 1 hour. Absolute bioavailability is about 100%. Food almost does not affect the absorption of levofloxacin.

Distribution. Approximately 30–40% of levofloxacin binds to plasma protein. The cumulative effect of levofloxacin with multiple doses of 500 mg once a day is practically absent. There is a slight, but expected cumulative effect after taking a dose of 500 mg 2 times a day. The equilibrium state is reached within 3 days.

Penetration into tissue and body fluids.

Penetration into the mucous membrane of the bronchi, bronchial secretion of lung tissue. C_max levofloxacin in the mucous membrane of the bronchi and bronchial secretions of the lungs after taking 500 mg orally was 8.3 μg / g and 10.8 μg / ml, respectively. These indicators were achieved within 1 hour after taking the drug.

Penetration into lung tissue. C_max levofloxacin in the lung tissues after ingestion of 500 mg orally was approximately 11.3 μg / g and was achieved 4-6 hours after administration of the drug. The concentration in the lungs exceeds that in plasma.

Penetration into the contents of the bubble. C_max levofloxacin 4.0–6.7 μg / ml in the contents of the bladder is reached 2–4 hours after taking the drug for 3 days in doses of 500 mg 1-2 times a day, respectively.

Penetration in the CSF. Levofloxacin poorly penetrates the CSF.

Penetration into the tissue of the prostate. With oral administration of 500 mg of levofloxacin 1 time per day for 3 days, the average concentration in the tissues of the prostate reached 8.7; 8.2 and 2.0 μg / g after 2, 6 and 24 hours, respectively; the average concentration coefficient of the prostate / blood plasma was 1.84.

Concentration in urine. The average concentration in the urine 8–12 hours after a single oral dose of 150, 300 or 500 mg of levofloxacin was 44; 91 and 200 mg / l, respectively.

Metabolism. Levofloxacin is slightly metabolized, the metabolites are desmethyl-levofloxacin and levofloxacin N-oxide. These metabolites make up less than 5% of the amount excreted in the urine. Levofloxacin is stereochemically stable and does not undergo chiral structure inversion.

After oral and iv administration, levofloxacin is excreted from the blood plasma relatively slowly (T_½ - 6-8 hours). It is usually excreted by the kidneys (85% of the administered dose).

There are no significant differences in the pharmacokinetics of levofloxacin after iv administration and oral administration, this suggests that these routes of administration (oral and iv) are interchangeable.

Patients with renal failure. The pharmacokinetics of levofloxacin are affected by renal failure. With impaired renal function, renal clearance and creatinine clearance decrease, and T_½ increases, as can be seen from the following table:

Elderly patients. There are no significant differences in the pharmacokinetics of levofloxacin in young patients and elderly patients, except for differences associated with creatinine clearance.

Gender differences. A separate analysis of female and male patients showed insignificant differences in the pharmacokinetics of levofloxacin depending on gender. There is no evidence that these differences are clinically significant.

Ornidazole

Suction. After oral administration, ornidazole is rapidly absorbed in the digestive tract. On average, absorption is 90%. C_max in blood plasma is reached within 3 hours

Distribution. The binding of ornidazole to plasma proteins is 13%. Ornidazole penetrates the CSF, other body fluids and tissues.

The concentration of ornidazole in blood plasma is in the range of 6–36 mg / l, that is, at a level that is considered optimal for various indications for use of the drug. After repeated use of doses of 500 mg and 1000 mg by healthy volunteers, every 12 hours the cumulation coefficient was 1.5–2.5.

Metabolism. Ornidazole is metabolized in the liver with the formation of mainly 2-hydroxymethyl and α-hydroxymethyl metabolites. Both metabolites are less active against Trichomonas vaginalis and anaerobic bacteria than unchanged ornidazole.

T_½ is about 13 hours. After a single application, 85% of the dose is excreted during the first 5 days, mainly in the form of metabolites. Approximately 4% of the dose taken is excreted by the kidneys unchanged.

Features of pharmacokinetics in certain disorders of the functioning of organs and systems.

Liver. T_½ the active substance in liver cirrhosis increases to 22 hours, clearance decreases (from 35 ml / min to 51 ml / min) compared with healthy individuals.

The kidneys. The pharmacokinetics of ornidazole does not change with impaired renal function, so the dose of the drug does not need to be changed. Ornidazole is excreted during hemodialysis. Before starting hemodialysis, it is necessary to use an additional 500 mg of ornidazole if the daily dose is 2 g per day, or an additional 250 mg of ornidazole if the daily dose is 1 g.

Indications

Treatment of mixed infections caused by pathogens (microorganisms and protozoa) that are sensitive to the components of the drug: infections of the genitourinary system, including acute and chronic pyelonephritis, prostatitis, trichomoniasis.

Application

Granazole is used in adults by mouth. tablets should be swallowed without chewing and drinking plenty of fluids. the drug can be taken both during and between meals.

The dose and duration of treatment depend on the sensitivity of microorganisms, the severity and type of infection. Dose for adults - 1 tablet of Grandazole 2 times a day for 5 days, then continue treatment with levofloxacin for 2-5 days. Treatment should be continued for at least 3 days after the disappearance of the clinical symptoms of the disease or after laboratory confirmation of the elimination of the pathogen.

The maximum daily dose is 4