Maksitsin

Maxicine is an antibacterial agent of the newest category. Included in the group of fourth generation fluoroquinolones.

Indications of the maksikina

It is indicated for the elimination of infections that are of bacterial origin and caused by microbial susceptible bacteria:

• with a non-hospital form of pneumonia (this also includes the types of disease that are caused by strains of microbes that have multiple resistance against antibiotics);
• infections, covering the subcutaneous layer and skin, and proceeding with complications (this includes the infected form of the diabetic foot syndrome);
• complicated infectious processes in the intra-abdominal area, including also polymicrobial infections (among them, the process of abscessing).

Release form

Produced in the form of a concentrate used in the manufacture of infusion solutions, in vials of 20 ml. With a bottle, one package also contains a solvent, which is contained in a 100 ml container.

Pharmacodynamics

Mechanisms that promote the resistance of microbes to inactivating agents (such as aminoglycosides with cephalosporins, as well as tetracyclines with penicillins and macrolides), do not affect the antibacterial properties of moxifloxacin. Cross-resistance between these antibiotics, as well as moxifloxacin was not found. Plasmid-mediated resistance has not yet been detected.

It is believed that the presence of a methoxy category in the meaning of C-8 increases activity, and also reduces the selectivity of resistant mutant strains of microbes from the group of gram-positive (in comparison with the C8-H category). At the value of C-7, an additional dicycloamine residue is observed, which prevents the active release of fluoroquinolones from cells of pathogenic microorganisms - this is the mechanism of development of resistance against fluoroquinolones.

In vitro tests have shown that resistance to moxifloxacin develops rather slowly. This is due to multiple mutations. There is also an extremely low frequency of occurrence of resistance (10-7-10-10). In the case of serial dilution of bacteria, only a slight increase in the MIC of the moxifloxacin appears.

Quinolones were characterized by cross-resistance, but individual anaerobes and Gram-positive bacteria, which are resistant to other quinolones, are susceptible to moxifloxacin.

Pharmacokinetics

With a one-time infusion of a solution of 400 mg, lasting 1 hour, the peak value reaches at the end of the procedure and is approximately 4.1 mg / L. This corresponds to an increase in the drug's level relative to its level with oral intake on average by 26%.

The AUC is 39 mg / hr and only slightly above the level after oral administration (35 mg · h / l). The bioavailability of the drug is approximately 91%.

After multiple infusions of medication intravenously (at a dosage of 400 mg) for 1 hour once a day, the minimum values, as well as the peak of the equilibrium plasma level are located in the gap, respectively, 4.1-5.9, and 0.43-0.84 mg / l. And with equilibrium indices, the drug AUC in the dosing interval is about 30% higher than the value after the first dose.

The average equilibrium value reaches 4.4 mg / l, and this value is observed at the end of infusion, lasting 1 hour.

The active ingredient passes a rapid distribution in the internal space of the body, outside the vessels. The drug level of AUC (normal value is 6 kg · h / l) is quite high at equilibrium values of the distribution volume (2 l / kg). The results revealed in in vitro tests, as well as ex vivo, showed values in the range of 0.02-2 mg / l.

Synthesis with blood protein (usually albumin) reaches 45%, and this ratio is not affected by drug concentrations. Although this is a fairly low level, the free component has high peak values (10 · IPC).

Moxifloxacin has high enough indices inside the tissues (for example, in the lungs - macrophages of the alveoli and epithelial fluid), and also inside the paranasal sinuses (polyps of the nose, latticular, and maxillary sinuses) and inflammatory foci in which the total values exceed the concentrations obtained inside plasma. Inside the intercellular fluid (in the subcutaneous and muscular tissues, and also in the saliva), the drug is found in large concentrations and in a free form that is not synthesized with the protein. Along with this, large medicinal values can be observed inside the fluids and tissues of the peritoneal organs, as well as inside the female genital organs.

The peak level, as well as the ratio of the indices inside the plasma and the infusion site, for the individual target tissues demonstrate similar data for each of the routes of use after using a single dosage of drugs (400 mg).

There is also biotransformation (phase 2) of moxifloxacin, followed by renal excretion (in addition, with bile / feces - unchanged or in the form of inactive elements M1 (sulfo compound), as well as M2 (glucuronides)).

In vitro experiments, and in addition, during clinical tests of the 1st phase, no metabolic interaction was observed with respect to pharmacokinetic parameters with other drugs, which take part in the biotransformation of the first phase using enzymes of the hemoprotein system P450.

Regardless of the method of administration, the decay products (M1 with M2) are observed inside the plasma at values lower than the unchanged element. In pre-clinical tests, both components were tested in commensurate sizes, so that the possible impact on the tolerability and safety of drugs was excluded.

Half-life is approximately 12 hours. The average level of total clearance when using 400 mg LS is in the range of 179-246 ml / minute. The clearance in the kidneys is approximately 24-53 ml / minute, from which it can be concluded that in the body there is a partial reabsorption of the drug - from the kidneys through the tubules.

Simultaneous administration of probenecid with ranitidine does not lead to a change in the values of the clearance of drugs in the kidneys.

Use of the maksikina during pregnancy

Maxicin can not be given to pregnant women.

Contraindications

Among the contraindications:

• the presence in humans of intolerance of any substance from the composition of the drug, or other antibiotics falling into the category of quinolones;
• the period of breastfeeding;
• children, as well as adolescents who are in the age of intensive growth.

Side effects of the maksikina

Use of the solution can cause such side effects:

• vomiting with nausea, as well as diarrhea (this may be a symptom of the pseudomembranous form of colitis) and the development of hyperbilirubinemia;
• dizziness with headaches, anxiety or general depression, severe fatigue, psychomotor agitation, development of psychosis, and sleep disorders;
• allergic manifestations - skin itch with a rash, facial swelling (or edema of the vocal cords), as well as the development of photosensitivity;
• the development of eosinophilia or agranulocytosis, and in addition leuko- or thrombocytopenia and an increase in the activity of the elements of AST and ALT;
• the appearance of nephrotic syndrome, occasionally - OPN;
• the development of tachycardia, arthralgia or myalgia, a decrease in blood pressure and a visual impairment.

[1]

Dosing and administration

For adults, a dose of 400 mg once a day is recommended for any type of infection. The recommended dosage should not be exceeded.

The duration of the therapeutic course is determined in accordance with the severity of the pathology, and in addition to the effectiveness of the drug.

At the beginning of therapy, it is required to use the medication in an infusion form, but later, if there are appropriate indications, it is permitted to prescribe it already in the form of tablets for oral administration.

Non-hospital type of pneumonia is treated with a stepwise method (first intravenous infusion and then oral administration of tablets), the total duration of which is 1-2 weeks.

When eliminating complicated infectious processes in the subcutaneous layer and skin, a stepwise method with a total course duration of 1-3 weeks is also used.

With complicated infections in the intra-abdominal region, stepwise treatment continues for 5-14 days.

It is forbidden to exceed the above-mentioned terms of therapeutic courses.

Information obtained as a result of clinical tests showed that the duration of the course with the use of tablets and infusion solution of LS reached a maximum of 21 days (during the elimination of infections in the subcutaneous layer and skin).

[2], [3]

Interactions with other drugs

Drugally significant interaction of the drug with such substances as probenecid, atenolol, theophylline with itraconazole, and moreover ranitidine, glibenclamide, calcium supplements, as well as morphine with oral contraceptives and digoxin has not been proved. When Maxicin is combined with the above drugs, dosage adjustment is not required.

Combination with warfarin does not change the pharmacokinetics of Maxycin, as well as PTV and other characteristics of blood coagulability.

Changes in the INR index - in people combining antibiotics (including moxifloxacin) with anticoagulants, there have been cases of increased anticoagulant activity. Among the risk factors are the age and state of human health, as well as infectious pathologies (with concomitant inflammation). Although there was no drug interaction with warfarin in clinical trials, people using concomitant treatment using drug data are required to monitor INR, and adjust the dose of oral anticoagulant if necessary.

The pharmacokinetic properties of digoxin slightly change under the action of moxifloxacin. With repeated use of the latter, volunteers showed an increase in peak digoxin values (approximately 30% at equilibrium), but without affecting the AUC level.

In the case of infusion of the solution intravenously, simultaneous use of activated carbon only slightly reduces the AUC value (by approximately 20%).

[4], [5], [6], [7]

Storage conditions

The solution is contained in a place that is closed from the sun and moisture, at temperatures not exceeding 25 ° C.

[8], [9], [10]

Shelf life

Maxicin can be used in the 2 years since the manufacture of the medicine.

[11]