Pharmacological properties

Pharmacodynamics

Tsefepim — a β-laktamny tsefalosporinovy antibiotic of iv of generation of a broad spectrum of activity for parenteral application. has bactericidal effect. it is active in relation to gram-positive and gram-negative bacteria, including the majority of the strains resistant to aminoglycosides or tsefalosporinovy antibiotics of iii of generation, such as ceftazidime. tsefepy vysokoustoychiv to influence of the majority β-лактамаз, quickly gets into gram-negative bacteria. extent of linking of a tsefepim with penitsillinsvyazyvayushchy protein rvr3 considerably exceeds affinity of other cephalosporins for parenteral application. the moderate affinity of a tsefepim in the relation rvr 1a and 1v also causes degree of its bactericidal activity. mbk (the minimum bactericidal concentration) / Mick (the minimum inhibiting concentration) for a tsefepim makes the relation less than 2 for more than 80% isolates of all sensitive gram-positive and gram-negative bacteria.

Tsefepim suppresses synthesis of enzymes of a wall of a bacterial cell. Drug has small affinity in the relation β-лактамаз which are coded by chromosomal genes.

concerning such microorganisms:

gram-positive aerobes: Staphylococcus aureus (including strains which produce β-lactamazu) and Staphylococcus epidermidis (including strains which produce β-lactamazu); other strains of stafilokokk (including S. hominis, S. saprophyticus), Streptococcus pyogenes (group A); Streptococcus agalactiae (group B); Streptococcus pneumoniae (including strains with average penicillin resistance — MIK from 0.1 to 1 mkg/ml); other β-hemolytic streptococci (the C, G groups, F), S. bovis (group D), Viridans group streptococci (the majority of strains of enterococci, for example, Enterecoccus faecalis, and staphylococcus, which rezistentna to Methicillinum, rezistentna to the majority of tsefalosporinovy antibiotics, including tsefepy);

gram-negative aerobes: Pseudomonas spp. (including P. aeruginosa, P. putida, P. Stutzeri) Escherichia coli, Klebsiella spp. (including K. pneumoniae, K. oxytoca, K. ozaenae), Enterobacter spp. (including E. cloacae, E. aerogenes, E. sakazakii), Proteus spp. (including P. mirabilis, P. vulgaris), Acinetobacter calcoaceticus (including subfamilies of Anitratus, Iwoffi); Aeromonas hydrophila, Capnocytophaga spp.; Citrobacter spp. (including C. diversus, C. freundii), Campylobacter jejuni; Gardnerella vaginalis; Haemophilus ducreyi; H. influenzae (including strains which produce β-lactamazu); H. Parainfluenzae; Hafnia alvei; Legionella spp.; Morganella morganii; Moraxella catarrhalis (Branhamella) catarrhalis (including strains which produce β-lactamazu); Neisseria gonorrhoeae (including strains which produce β-lactamazu); N. meningitidis; Providencia spp. (including P. rettgeri, P. stuartii); Salmonella spp.; Serratia (including S. marcescens, S. liquefaciens); Shigella spp.; Yersinia enterocolitica.

rather many strains of Xanthomonas (Pseudomonas) maltophilia;

anaerobe bacterias: Bacteroides spp., including B. melaninogenicus and other microorganisms of an oral cavity which belong to Bacteroides; Clostridium perfringens; Fusobacterium spp.; Mobiluncus spp.; Peptostreptococcus spp.; Veillonella spp.

concerning Bacteroides fragilis and Clostridium difficile.

Tsefepim is completely soaked up by

after introduction in oil.

Average concentration of a tsefepim in blood plasma at adult healthy men through different time after disposable in/in and introductions in oil are given by

in tab. 1.

Table 1. Concentration of a tsefepim in blood plasma (mkg/ml) at in/in and introduction in oil

Dose of a tsefepim	0.5 h	1 h	2 h	4 h	8 h	12 h
1 g in/in	38.2	21.6	11.6	5	1.4	0.2
	78.7	44.5	24.3	10.5	2.4	0.6
	163.1	85.8	44.8	19.2	3.9	1.1
1 in oil	8.2	12.5	12	6.9	1.9	0.7
	14.8	25.9	26.3	16.0	4.5	1.4
	36.1	49.9	51.3	31.5	8.7	2.3

In urine, bile, peritoneal liquid, mucous secretion of bronchial tubes, a phlegm, a prostate, an appendix and a gall bladder also reach therapeutic concentration of a tsefepim.

On average T _½ tsefepima makes about 2 h of an organism and does not depend on a dose in the range of 250 mg — 2 g. At a dose up to 2 g in/in with an interval of 8 h within 9 days the cumulation of medicine in an organism is noted.

Tsefepim is metabolized by

to N-metilpirrolidina which quickly turns into N-metilpirrolidina oxide. Tsefepim is allocated mainly by glomerular filtration (the general clearance of a tsefepim is about 120 ml/min., average hepatic clearance — 110 ml/min.). With urine about 80-85% of a dose in the form of not changed tsefepim, are removed by 1% of N-metilpirrolidina, about 6.8% of N-metilpirrolidina oxide and about 2.5% of an epimer of a tsefepim. Linking of a tsefepim with proteins of blood plasma makes less than 19% and does not depend on concentration of medicine in blood plasma.

At patients 65 years with normal function of kidneys are aged more senior than

medicine dose adjustment is not required.

At patients with a renal failure of T _½ tsefepima increases, at the same time the linear dependence between the general clearance of medicine and clearance of creatinine is observed. The t _½ at patients with heavy renal failures which need treatment by a hemodialysis makes 13 h, and at continuous out-patient peritoneal dialysis — 19 h. At patients with abnormal function of kidneys the dose should be selected individually.

Pharmacokinetics of a tsefepim at patients from the liver broken by function or a mucoviscidosis does not change. Dose adjustment for such patients is not required.

Children. Researches of pharmacokinetics of a tsefepim were conducted with participation of children aged from 2 months up to 11 years after one-time administration or several administrations of medicine by each 8 h and each 12 h. After disposable in/in an injection the general clearance of an organism and distribution volume in steady state on average was 3.3 (1.0) ml/min. and 0.3 (0.1) l/kg with