The quinolone group includes. Quinolones I generation. Application in clinical practice.

  Fluoroquinolones:

Fluoroquinolones:

modern concept of application

Shchekina EG, Ph.D. farm Sciences, Associate Professor Pharmacology of NUF

Antibacterial drugs of the quinolone group have been known for a long time. The ancestor of the group is chloroquine, and the first quinolone introduced into medical practice is nalidixic acid, synthesized in 1962.

In the following years, oxolinic, pipimedic, and pyromidic acids, as well as cinoxacin, were created. The lack of systemic action and a narrow spectrum (some gram-negative microorganisms) limited the use of quinolones at this time as uro-antiseptics for urinary tract infections. The inclusion of fluorine atoms in the 6th position of the quinolone molecule significantly expanded the spectrum of their antibacterial action. Currently, more than 30 fluoroquinolones have been obtained, active compounds that do not contain fluorine in the 6th position — desfluoroquinolones (for example, Garenoxacin, which is in the final stages of clinical trials) have appeared. The development scheme of this pharmacological group is shown in Fig. one.

There is no generally accepted systematization of fluoroquinolones. There are several classifications: fluoroquinolones are divided by generations (Table 1); according to the number of fluorine atoms in the molecule (monofluoroquinolones, difluoroquinolones and trifluoroquinolones); as well as fluorinated and anti-pneumococcal (or respiratory). The most studied and widely used in the clinic are monofluorinated compounds.

Characteristic features of this group of drugs are a unique mechanism. antimicrobial action, in excess of wide range  and a powerful bactericidal effect, the presence of a post-antibiotic effect, low toxicity, high bioavailability when taken orally, good penetration into the tissues and cells of the microorganism, a long half-life and slow development of resistance of microorganisms.

The target of the fluoroquinolone action is bacterial topoisomerases - topoisomerase IV and DNA gyrase (topoisomerase II) - enzymes that super-spiral the spatial DNA molecule at various stages of its replication. Fluoroquinolones inhibit topoisomerase IV and bacterial DNA synthesis, which leads to disruption of the biosynthesis of DNA and RNA and an irreversible disruption of protein synthesis in a microbial cell. As a result of the action of fluoroquinolones, the aggressive properties of bacteria are reduced, the induction of exotoxins and exoenzymes is suppressed, and the sensitivity of microorganisms to phagocytosis is increased. It is worth noting that the drugs have the ability to act on microorganisms in the period of growth and rest.

Fluoroquinolones have an ultra-wide spectrum of action. Preparations of this group are active against gram-positive and gram-negative, aerobic and anaerobic microorganisms, chlamydia, mycoplasmas, legionella, mycobacteria. Sensitive to fluoroquinolones Gy (-) rods: tsitrobakter, Enterobacteriaceae, Campylobacter, Escherichia, Salmonella, Serratia, Morganella, Shigella, vibrio, Proteus (including mirabelny vulgar..), Klebsiella, Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella Catarralis, Providencia, Pasteurella, Brucella, Neisseria, all kinds of staphylococci. Preparations of the first generation are active against a wide range of gram-negative aerobic microorganisms (including those with multiple resistance) and Staphylococcus aureus. Ciprofloxacin, ofloxacin and lomefloxacin inhibit the growth of Mycobacterium tuberculosis and leprosy. The disadvantage of drugs I generation is their low activity against pneumococci, chlamydia, mycoplasmas and anaerobes. Fluoroquinolones of the II and III generations are not inferior to the drugs of the 1st generation in their effect on gram-negative microorganisms (except for the pseudomonas aeruginosa). As for the gram-positive flora, including pneumococci, chlamydia, mycoplasma, mycobacteria, the effect of preparations of the II and III generations of fluoroquinolones significantly exceeds the action of their predecessors. Levofloxacin, sparfloxacin, moxifloxacin and sitafloxacin are characterized by an increased affinity for topoisomerase of gram-positive bacteria and, as a result, greater antibacterial activity, therefore they are distinguished in the group of "respiratory fluoroquinolones". Preparations of the third generation are effective against spore-forming anaerobes, including those resistant to the action of fluoroquinolones of the first generation. By activity in relation to gram-negative aerobic microorganisms, they are inferior to ciprofloxacin. Gatifloxacin is considered as a promising drug for inclusion in the combined therapy of tuberculosis. All fluoroquinolones are resistant to the action of β-lactamase gram-negative and gram-positive bacteria, but only trovafloxacin and moxifloxacin act on methicillin-resistant staphylococci. Fluoroquinolone resistant to fungi, viruses, treponema and most of the simplest. There is evidence that fluoroquinolones have an immunomodulatory effect, increase the phagocytic activity of neutrophils.

Noteworthy are the pharmacokinetic characteristics of this group of drugs. Fluoroquinolones are characterized by a large volume of distribution, good penetration into tissues and low binding to plasma proteins. Bioavailability for most fluoroquinolones when administered orally is 80–100%, except for norfloxacin (20–40%). All fluoroquinolones are rapidly absorbed in the digestive tract. Ofloxacin, pefloxacin and lomefloxacin are best absorbed. Food slows down the absorption of drugs, but does not reduce their bioavailability. The maximum concentration in the blood is reached in 1-3 hours. Fluoroquinolones penetrate well into tissues and body fluids, alveolar macrophages, polymorphonuclear leukocytes, biliary and airways, lungs, gastrointestinal mucosa, kidneys, genitals. Worse drugs penetrate cerebrospinal fluidhowever, with meningitis, the penetration rate increases (especially for pefloxacin). The concentration of fluoroquinolones inside the cells is usually several times higher than in the blood plasma. Pefloxacin is metabolized to the greatest extent (up to 80%), while its main metabolite, norfloxacin, retains antibacterial activity. Other fluoroquinolones are less metabolized, but their metabolites are inactive. The elimination half-life for most drugs of the first generation is 5–9 hours, and for new fluoroquinolones - 10–20 hours. Such a long half-life, as well as the post-antibiotic effect, allows to prescribe drugs of the first generation 2 times, and drugs of the second and third generations - 1 time per day.

The mechanism of removal of drugs in this group can be renal and extrarenal. In case of renal insufficiency, it is necessary to adjust the dose of ciprofloxacin, sparfloxacin, ofloxacin and levofloxacin.

The pharmacokinetic properties of fluoroquinolones allow them to be used in almost any localization of the infectious process (Table 2).

One of the most effective fluoroquinolones against gram-negative microorganisms, including against pyocyanic stick, is ciprofloxacin. The drug is also used in the combination therapy of drug-resistant forms of tuberculosis.

The most active fluoroquinolone I of generation against chlamydia and pneumococci is ofloxacin. It is used in combination therapy for drug-resistant forms of tuberculosis.

Pefloxacin is slightly inferior to ciprofloxacin, ofloxacin and levofloxacin in activity, but it penetrates the BBB better than other fluoroquinolones.

Norfloxacin is used in the treatment of urogenital infections, but more often than other fluoroquinolones causes side effectsFirst of all, from the gastrointestinal tract and central nervous system.

Lomefloxacin is inactive against pneumococci, chlamydia, mycoplasma. It is used as part of a combination therapy for tuberculosis.

Levofloxacin is a levorotatory isomer of ofloxacin. Twice as active and better tolerated than ofloxacin. The drug is highly active against penicillin-resistant pneumococci, enterococci, chlamydia, mycoplasma, golden and epidermal staphylococci, the causative agent of gas gangrene. In relation to Pseudomonas aeruginosa inferior to ciprofloxacin. Among the last-generation fluoroquinolones, levofloxacin is still the only drug available in two dosage forms - for oral administration and for intravenous.

Sparfloxacin is close in spectrum to levofloxacin, but is worse tolerated by patients. Highly active against Mycobacterium tuberculosis.

Moxifloxacin inhibits the activity of two target enzymes simultaneously; therefore, it has a high bactericidal activity and an increased ability to prevent the appearance of resistant strains. The effect on mycoplasma and ureaplasma is superior to ciprofloxacin and levofloxacin, and on the effect on chlamydia - ciprofloxacin and ofloxacin. The effectiveness of the drug against spore-forming anaerobes is comparable to imipenem, metronidazole and clindamycin. By the strength of the anti-pneumococcal effect, it is inferior only to sitafloxacin and hemifloxacin.

Gatifloxacin has comparable activity to ciprofloxacin against pathogens of atypical pneumonia. By activity against intracellular pathogens, gatifloxacin is ahead of modern macrolides azithromycin and roxithromycin.

Hemifloxacin is more active on gram-positive microorganisms than moxifloxacin, gatifloxacin, sitafloxacin and first-generation drugs. Remains active against pneumococci resistant to ciprofloxacin and gram-negative bacteria, highly active against atypical pneumonia pathogens. Sitafloxacin and hemifloxacin are among the most active anti-pneumococcal fluoroquinolones.

Spectrum of action trovafloxacincomparable to the spectrum of imipenem, the activity of the drug against a number of strains of Pseudomonas aeruginosa exceeds the activity of ciprofloxacin.

  Table 2. Indications for use, rational choice and interchangeability of fluoroquinolones

	Nor-Flock Satsin	Oflock Satsin	Cipro-flock Satsin	Peflock Satsin	Lome Flock Satsin	Left-flock Satsin	Spar Flock Satsin	Moxy flock sacin	Hemi Flock Satsin	Gati flock saqing	Sita Flock Satsin	Throve-flock-satsin
Urinary tract infections	+	+	+		+	+
Respiratory tract infections		+	+	+	+	+	+	+	+	+	+	+
Infections of bones and joints		+	+	+	+	+		+
Skin and soft tissue infections		+	+	+	+	+	+	+
Intestinal infections			+	+	+
Intraabdominal infections and sepsis		+	+	+								+
Gonorrhea	+	+	+	+
Meningitis		+	+	+		+
Prostatitis	+	+		+
Tuberculosis		+	+		+					+
Endocervical and urethral chlamydial infections		+
Wound and burn infections		+	+									+

Fluoroquinolones are low-toxic drugs. The development of adverse reactions that require discontinuation of treatment is noted in 1-3% of patients. Among side effects  groups most often mark reactions from the gastrointestinal tract (3–6%) - nausea, changes in taste, diarrhea, abdominal pain, etc .; from the central nervous system (1–4%) - headache, dizziness, irritability, attention disorders, sleep disturbances, ototoxicity, seizures may develop. Adverse effects of the liver are observed in 2-3% of patients and are manifested by increased levels of serum transaminases and alkaline phosphatase, hepatitis, liver failure, cholestatic jaundice. Hepatotoxic action most often occurs when using the latest generation of fluoroquinolones, in particular, trovafloxacin, which caused its withdrawal from the market in Europe.

0.5–2% of patients taking fluoroquinolones allergic reactions, more characteristic of intravenous administration (anaphylactic shock). Fluoroquinolones have phototoxicity, especially sparfloxacin and lomefloxacin. The development of the photoelectric effect is explained by the possible destruction of the fluoroquinolone molecule under the influence of UV radiation, the induction of free radicals and, as a result, skin damage. Therefore, you can not be exposed to UV rays during treatment with fluoroquinolones and for 3 days after the course of therapy.

When fluoroquinolones are used, tendinitis and tendovaginitis are possible due to impaired peptidoglycan synthesis in the tendon structure, therefore, in some cases, it is necessary to cancel the drug, especially pefloxacin, due to the possibility of tendon ruptures (more often in elderly people). With the simultaneous appointment of fluoroquinolones with glucocorticoids, the risk of tendon ruptures increases. Fluoroquinolones are not prescribed to children under the age of 18 because of the risk of developing pathological changes in the cartilage tissue. Due to the insufficient knowledge of the drugs, the use of fluoroquinolones during pregnancy and lactation is not recommended. There is no data on teratogenicity of fluoroquinolones in the literature.

After instillation of drugs, there may be short-term burning, conjunctival hyperemia, eyelid edema, tearing, photophobia, keratitis. Rarely pseudomembranous colitis, secondary candidiasis, transient interstitial nephritis. In the process of treatment with fluoroquinolones, patients should consume a large amount of fluid to prevent crystalluria (1.2–1.5 l / day).

Hemolytic anemia can develop in patients with a deficiency of glucose-6-phosphate dehydrogenase, especially when using ciprofloxacin, pefloxacin, norfloxacin, sparfloxacin.

Cardiotoxicity in the form of prolongation of the QT interval on the ECG is more common in fluoroquinolones III - IV generation. This effect and, possibly, the cases of sudden death associated with it were the basis for excluding grepafloxacin from medical practice. Fluoroquinolones should be prescribed with caution to people suffering from severe cardiovascular pathology, as well as when combining these drugs with drugs that cause prolongation of the QT interval: antiarrhythmic (quinidine, sotalol, amiodarone), antihistamine (terfenadine, astemizole), psychotropic (fluoxetine), macrolide, terroladine (terfenadine, astemizole), psychotropic (fluoxetine), macrololide (terfenadine, astemizole), psychotropic (fluoxetine), macrololide (terfenadine, astemizole), psychotropic (fluoxetine), macrololide (terfenadine, astemizole), psychotropic (fluoxetine), makrolida, , co-trimoxazole, imidazoles and quinolone-like antimalarial drugs.

Fluoroquinolones should not be administered to patients with convulsive syndrome, parkinsonism, epilepsy, cerebral circulation disorders and renal failure.

Fluoroquinolones inhibit the oxidative enzymes of the liver and can enhance the effect of drugs that are metabolized by the cytochrome P450 system (xanthines, indirect anticoagulants). When co-prescribing fluoroquinolones with urine alkalizing drugs (carbonic anhydrase inhibitors, citrates, sodium bicarbonate), the risk of nephrotoxicity and crystalluria increases. The antimicrobial effect of fluoroquinolones is reduced when they are simultaneously administered with antibacterial agents that violate the synthesis of nucleic acids (tetracycline, rifampicin, nitrofurans) and protein (levomycetin). Fluoroquinolones should not be used simultaneously with iron supplements, multivitamins, antacids (containing aluminum or magnesium), ranitidine and pirenzepine.

Thus, fluoroquinolones are highly effective in treating a wide range of community-acquired and nosocomial infections and can be used as an empirical therapy for severe infections in the hospital. Currently, they are considered as a serious alternative to highly active broad-spectrum antibiotics in the treatment of severe infections.

L I T E R A T U R A

1. Vengerovsky A. I. Lectures on pharmacology for doctors and pharmacists. - 3rd ed., Pererab. and additional: a tutorial. - M .: IF “Physical and mathematical literature”, 2007. - 704 p.

2. Drogovoz S.M., Strashny V.V. Pharmacology for the supplement of licorice, provisor and student. - 2006. - 479 p.

3. Clinical Pharmacology: Textbook. / Under. ed. Kukes - 3rd ed., Pererab. and add. - M .: GEOTAR-Media, 2006 p.

4. Mashkovsky M.D. Medicines. - 15th ed., Peregat. and add. - M .: LLC "Publishing New Wave", 2005. - 1200 p.

5. Mikhailov I. B. Physician's table book on clinical pharmacology. - A guide for doctors. - SPb .: Foliant Publishing House, 2001. - 736 p.

6. Sidorenko S.V. The role of quinolones in antibacterial therapy / / Russian Medical Journal. - 2003. - V. 11. - № 2. - P. 98–102.

7. Kharkevich D.A. Pharmacology: Textbook. - 8th ed., Pererab., Ext. and rev. - M .: GEOTAR-Media, 2005. - P. 373–376.

Drugs of the quinolone class used in clinical practice since the early 60s, according to the mechanism of action, are fundamentally different from other AMPs, which ensures their activity against resistant, including multiresistant, microorganism strains. The quinolone class includes two main groups of drugs that differ fundamentally in structure, activity, pharmacokinetics and breadth of indications for use: non-fluorinated quinolones and fluoroquinolones. Quinolones are classified according to the time of introduction of new drugs with improved antimicrobial properties into practice. According to the working classification proposed by R. Quintiliani (1999), quinolones are divided into four generations:

Quinolone classification

I generation:

Nalidixic acid

Oxolinic acid

2nd generation:

Lomefloxacin

Norfloxacin

Ofloxacin

Pefloxacin

Ciprofloxacin

III generation:

Levofloxacin

Sparfloxacin

IV generation:

Moxifloxacin

The listed drugs are registered in Russia. Some other drugs of the quinolone class, mainly fluoroquinolones, are also used abroad.

Generation I quinolones are predominantly active against gram-negative flora and do not create high concentrations in blood and tissues.

Fluoroquinolones, approved for clinical use since the early 80s (II generation), have a wide spectrum of antimicrobial action, including staphylococcus, high bactericidal activity and good pharmacokinetics, which allows them to be used for the treatment of infections of various localization. Fluoroquinolones, introduced into practice since the mid-90s (III-IV generation), are characterized by higher activity against gram-positive bacteria (primarily pneumococci), intracellular pathogens, anaerobes (IV generation), and also more optimized pharmacokinetics. The presence of a number of drugs dosage forms for intravenous administration and oral administration in combination with high bioavailability allows for step therapy, which, with comparable clinical efficacy, is significantly cheaper than parenteral.

The high bactericidal activity of the fluoroquinolones made it possible to develop for a number of drugs (ciprofloxacin, ofloxacin, lomefloxacin, norfloxacin) dosage forms  for local application  in the form of eye and ear drops.

Mechanism of action

Quinolones have a bactericidal effect. Inhibiting two vital microbial cell enzymes, DNA gyrase and topoisomerase IV, disrupt DNA synthesis.

Activity spectrum

Non-fluorinated quinolones act primarily on gram-negative bacteria of the family Enterobacteriaceae
(E. coli, Enterobacter  spp., Proteus  spp., Klebsiella  spp., Shigella  spp., Salmonella  spp.) as well Haemophillus  spp. and Neisseria  spp. Oxolinic and pipemidovy acids, besides, are active in the relation S.aureus  and some strains P.aeruginosabut it has no clinical significance.

Fluoroquinolones have a much wider spectrum. They are active against a number of gram-positive aerobic bacteria ( Staphylococcus  spp.), most strains are gram negative, including E. coli  (including enterotoxigenic strains), Shigella  spp., Salmonella  spp., Enterobacter  spp., Klebsiella  spp., Proteus  spp., Serratia  spp., Providencia  spp., Citrobacter  spp., M.morganii, Vibrio  spp., Haemophilus  spp., Neisseria  spp., Pasteurella  spp., Pseudomonas  spp., Legionella  spp., Brucella  spp., Listeria  spp.

In addition, fluoroquinolones, as a rule, are active against quinolone resistant bacteria of the first generation. Fluoroquinolones III and, especially, IV generation are highly active against pneumococci, more active than II generation drugs against intracellular pathogens ( Chlamydia  spp., Mycoplasma  spp., M.tuberculosis, fast-growing atypical mycobacteria ( M.avium  and others), anaerobic bacteria (moxifloxacin). This does not decrease the activity against gram-negative bacteria. An important property of these drugs is activity against a number of bacteria resistant to fluoroquinolones II generation. Due to their high activity against pathogens of bacterial infections VDP and NDP, they are sometimes called “respiratory” fluoroquinolones.

AT varying degrees  fluoroquinolones are enterococci sensitive, Corynebacterium  spp.,   Campylobacter  spp.,   H.pylori, U.urealyticum.

Pharmacokinetics

All quinolones are well absorbed in the digestive tract. Food may slow down the absorption of quinolones, but does not have a significant effect on bioavailability. Maximum blood concentrations are reached on average 1-3 h after ingestion. The drugs pass the placental barrier, and in small quantities penetrate into breast milk. Excreted mainly by the kidneys and create high concentrations in the urine. Partially excreted in the bile.

Quinolones I generation do not create therapeutic concentrations in the blood, organs and tissues. Nalidixic and oxolinic acids undergo intensive biotransformation and are derived mainly in the form of active and inactive metabolites. Pipemidovy acid is a little metabolized and removed in not changed look. The half-life of nalidixic acid is 1–2.5 hours, pipemidoic acid — 3–4 hours, oxolinic acid — 6–7 hours. Maximum concentrations in urine are generated on average after 3–4 hours.

In the event of a renal failure, the elimination of quinolones slows down significantly.

Fluoroquinolones, unlike non-fluorinated quinolones, have a large volume of distribution, create high concentrations in organs and tissues, penetrate into the cells. The exception is norfloxacin, the highest levels of which are noted in the intestine, MVP and prostate gland. The highest tissue concentrations reach ofloxacin, levofloxacin, lomefloxacin, sparfloxacin, moxifloxacin. Ciprofloxacin, ofloxacin, levofloxacin and pefloxacin pass through the BBB, reaching therapeutic concentrations.

The degree of metabolism depends on the physicochemical properties of the drug: pefloxacin is most actively biotransformed, lomefloxacin, ofloxacin, and levofloxacin are the most active. From feces, 3-4% to 15-28% of the received dose is eliminated.

Bacterial infections in patients with cystic fibrosis.

Tuberculosis (ciprofloxacin, ofloxacin and lomefloxacin in combination therapy for drug-resistant tuberculosis).

Norfloxacin, taking into account the features of pharmacokinetics, it is used only for intestinal infections, infections of the urinary tract and prostatitis.

Contraindications

For all quinolones

Allergic reaction to quinolone preparations.

Deficiency of glucose-6-phosphate dehydrogenase.

Pregnancy.

Additionally for quinolones I generation

Severe abnormal liver and kidney function.

Severe cerebral atherosclerosis.

Additionally for all fluoroquinolones

Childhood.

Lactation.

Warnings

Allergy.  Cross to all quinolone preparations.

Pregnancy  There are no reliable clinical data on the toxic effects of quinolones on the fetus. There are isolated reports of hydrocephalus, increased intracranial pressure and bulging of fontanelles in newborns whose mothers took nalidixic acid during pregnancy. In connection with the development in the experiment of arthropathy in immature animals, the use of all quinolones during pregnancy is not recommended.

Lactation. Quinolones in small amounts penetrate into breast milk. There are reports of hemolytic anemia in newborns whose mothers took nalidixic acid during breastfeeding. In the experiment, quinolones caused arthropathy in immature animals, therefore, when prescribing them to nursing mothers, it is recommended to transfer the child to artificial feeding.

Pediatrics  On the basis of experimental data, the use of quinolones is not recommended during the period of formation of the osteo-articular system. Oxolinic acid is contraindicated in children under 2 years old, pipemidovaya - up to 1 year, nalidixic - up to 3 months.

Fluoroquinolones are not recommended for children and adolescents. However, the existing clinical experience and special studies on the use of fluoroquinolones in pediatrics did not confirm the risk of damage to the osteo-articular system, and therefore fluoroquinolones can be prescribed for children according to their vital indications (aggravation of infection with cystic fibrosis; severe infections of various localization caused by multi-resistant strains of bacteria; infections with neutropenia ).

Geriatrics  In older people, there is an increased risk of tendon rupture when using fluoroquinolones, especially in combination with glucocorticoids.

Diseases of the central nervous system.  Quinolones have a stimulating effect on the central nervous system, so they are not recommended for use in patients with a history of convulsive disorder. The risk of seizures increases in patients with cerebral circulation disorders, epilepsy and parkinsonism. When using nalidixic acid may increase intracranial pressure.

Impaired renal function and liver.  Generation I quinolones cannot be used in case of renal and hepatic insufficiency, since, due to the accumulation of drugs and their metabolites, the risk of toxic effects increases. Doses of fluoroquinolones with severe renal failure are subject to correction.

Acute porphyria.  Quinolones should not be used in patients with acute porphyria, as they have a porphyrinogenic effect in animal experiments.

Drug interactions

With simultaneous use with antacids and other drugs containing ions of magnesium, zinc, iron, bismuth, the bioavailability of quinolones may be reduced due to the formation of nonabsorbable chelate complexes.

Pipemidic acid, ciprofloxacin, norfloxacin and pefloxacin can slow down the elimination of methylxanthines (theophylline, caffeine) and increase the risk of their toxic effects.

The risk of the neurotoxic effects of quinolones is increased when used together with NSAIDs, nitroimidazole derivatives and methylxanthines.

Quinolones show antagonism with nitrofuran derivatives, therefore combinations of these drugs should be avoided.

Generation I quinolones, ciprofloxacin and norfloxacin can interfere with the metabolism of indirect anticoagulants in the liver, which leads to an increase in prothrombin time and the risk of bleeding. With simultaneous use may require correction of the dose of anticoagulant.

Fluoroquinolones should be prescribed with caution at the same time as drugs that prolong the QT interval, as the risk of cardiac arrhythmias increases.

With simultaneous use with glucocorticoids increases the risk of tendon rupture, especially in the elderly.

When using ciprofloxacin, norfloxacin and pefloxacin together with urine alkalizing drugs (carbonic anhydrase inhibitors, citrates, sodium bicarbonate), the risk of crystalluria and nephrotoxic effects increases.

With simultaneous use with azlocillin and cimetidine due to a decrease in tubular secretion, the elimination of fluoroquinolones is slowed down and their concentration in the blood increases.

Patient Information

Drugs quinolone when ingestion should be taken with a full glass of water. Take at least 2 hours before or 6 hours after taking antacids and preparations of iron, zinc, bismuth.

Strictly adhere to the regimen and regimen of treatment during the entire course of therapy, do not skip the dose and take it at regular intervals. If you miss a dose, take it as soon as possible; Do not take if it is almost time to take the next dose; do not double the dose. To withstand the duration of therapy.

Do not use drugs that have expired.

During the period of treatment to observe an adequate water regime (1.2-1.5 l / day).

Do not be exposed to direct sunlight and ultraviolet rays during the use of drugs and for at least 3 days after the end of treatment.

Consult a doctor if improvement does not occur within a few days or new symptoms appear. If pain in the tendons occurs, ensure that the affected joint is at rest and consult a doctor.

Table. Preparations of the quinolone / fluoroquinolone group.
Main characteristics and features of the application

INN	Lekforma LS	F (inside),%	T ½, h *	Dosing regimen	Drug Features
Quinolones I generation (non-fluorinated)
Nalidixic acid	Caps. 0.5 g Tab. 0.5 g	96	1-2,5	Inside Adults: 0.5-1.0 g every 6 hours Children older than 3 months: 55 mg / kg per day in 4 divided doses	Only active against gram-negative bacteria. Not used in acute pyelonephritis due to low concentrations in the kidney tissue. With the appointment of more than 2 weeks, the dose should be reduced by 2 times, monitor the function of the kidneys, liver and blood picture
Oxolinic (oxolinic) acid	Tab. 0.25 g	ND	6-7	Inside Adults: 0.5-0.75 g every 12 hours Children over 2 years old: 0.25 g every 12 hours	- variable absorption in the digestive tract; - longer T ½; - worse tolerated
Pipemidovaya (pipemidievy) acid	Caps. 0.2 g; 0.4 g Tab. 0.4 g	80-90	3-4	Inside Adults: 0.4 g every 12 hours Children older than 1 year: 15 mg / kg / day in 2 doses	Differences from nalidixic acid: - a wider range; - longer T ½
Quinolones II - IV generations (fluoroquinolones)
Ciprofloxacin	Tab. 0.25 g; 0.5 g; 0.75 g; 0.1 g Rr d / inf. 0.1 and 0.2 g per bottle. 50 ml and 100 ml of Conc. d / inf. 0.1 g in amp. on 10 ml Eye / ear cap 0.3% Eye. ointment 0.3%	70-80	4-6	Inside Adults: 0.25-0.75 g every 12 hours; within 3 days; for acute gonorrhea - 0.5 g once In / in Adults: 0.4-0.6 g every 12 hours Locally	The most active fluoroquinolone against most gram-negative bacteria Surpasses other fluoroquinolones in activity against P.aeruginosa Used in combination therapy for drug-resistant tuberculosis.
Ofloxacin	Tab. 0.1 g; 0.2 g Rr d / inf. 2 mg / ml per vial. Eye / ear cap 0.3% Eye. ointment 0,3 %	95-100	4,5-7	Inside for acute cystitis in women - 0.1 g every 12 hours within 3 days; with acute gonorrhea - 0.4 g once In / in Adults: 0.2-0.4 g / day in 1-2 administrations Injected by slow infusion over 1 h Locally Ushn cap instill 2-3 cap. in the affected ear 4-6 times a day, with severe course  - every 2-3 hours, gradually trimming as it improves Eye. ointment lay for the lower eyelid of the affected eye 3-5 times a day	The most active fluoroquinolone II generation against chlamydia and pneumococci. It has little effect on the metabolism of methylxanthines and indirect anticoagulants. Used as part of combination therapy. drug-resistant tuberculosis
Pefloxacin	Tab. 0.2 g; 0.4 g Rr d / in. 0.4 g in amp. on 5 ml Rr d / in. 4 mg / ml in vial. on 100 ml	95-100	8-13	Inside Adults: 0.8 g at the first dose, then 0.4 g every 12 hours; in acute cystitis in women and in acute gonorrhea - 0.8 g once In / in Adults: 0.8 g for the first administration, then 0.4 g every 12 hours Injected by slow infusion over 1 h	Somewhat inferior in activity in vitro  cipro-floxacin, ofloxacin, levofloxacin. Better than other fluoroquinolones penetrates through the BBB. Forms active metabolite - norfloxacin
Norfloxacin	Tab. 0.2 g; 0.4 g; 0.8 g Eye / ear cap 0.3% per bottle. on 5 ml	30-70	3-4	Inside Adults: 0.2–0.4 g every 12 hours; for acute cystitis in women - 0.4 g every 12 hours within 3 days; with acute gonorrhea - 0.8 g once Locally Eye. cap instill 1-2 cap. in the affected eye every 4 hours; in case of severe course, every hour until improvement. Ushn cap instill 2-3 cap. in the affected ear 4-6 times a day, in severe cases - every 2-3 hours, gradually trimming as it improves	It is used systematically only for the treatment of infections of the IMP, prostatitis, gonorrhea and intestinal infections  (shigellosis). Locally - for infections of the eye and outer ear
Lomefloxacin	Tab. 0.4 g Eye. cap 0.3% per bottle. on 5 ml	95-100	7-8	Inside Adults: 0.4-0.8 g / day in 1-2 doses Locally Eye. cap instill 1-2 cap. in the affected eye every 4 hours, in severe cases - every hour until improvement	Low active against pneumococcus, chlamydia, mycoplasma. It is used in combination therapy for drug-resistant tuberculosis. More often than other fluoroquinolones, causes photodermatitis. Does not interact with methylxanthines and indirect anticoagulants
Sparfloxacin	Tab. 0.2 g	60	18-20	Inside Adults: on the first day, 0.4-0.2 g at one time, on subsequent days, 0.1-0.2 g 1 time per day	The spectrum of activity is close to levofloxacin. Highly active against mycobacteria. Surpasses other fluoroquinolones in duration of action. More often than other fluoroquinolones, causes photodermatitis. Does not interact with methylxanthines.
Levofloxacin	Tab. 0.25 g; 0.5 g Rr d / inf. 5 mg / ml per vial. by 100 ml	99	6-8	Inside Adults: 0.25-0.5 g every 12-24 h; with acute sinusitis - 0.5 g 1 time per day; with pneumonia and severe forms  infections - 0.5 g every 12 hours In / in Adults: 0.25-0.5 g every 12-24 h, with severe forms 0.5 g every 12 h Enter by slow infusion over 1 h	Levorotatory isomer ofloxacin. Twice more active in vitrothan ofloxacin, including against gram-positive bacteria, chlamydia, mycoplasmas and mycobacteria. Better tolerated than ofloxacin
Moxifloxacin	Tab. 0.4 g	90	12	Inside Adults: 0.4 g once per day	Surpasses other fluoroquinolones in anti-pneumococcal activity, including multi-resistant; chlamydia, mycoplasma, anaerobes. Does not interact with methylxanthines

* With normal kidney function