What Is Cefepime?

Cefepime chemical name 1-[[((6R, 7R) -7- [2- (2-amino-4-thiazolyl) -glyoxylamido] -2-carboxy-8-oxo- 5-thia-1-azabicyclo [4,2,0] oct-2-en-3-yl] methyl] -1-methylpyrrolidine chloride, 72- (Z)-(O-methyl Oxime), white or almost white crystalline powder, melting point 150 ° C (decomposed). UV maximum absorption (pH = 7 phosphate buffer): 235, 257 nm (16700, 16100). The molecular formula is C19H24N6O5S2 and the molecular weight is 480.56100.

Chinese name: Cefepime
English name: Cefepime
nickname: Cefpodam, Cefepim
Chemical formula: C19H24N6O5S2
Molecular weight: 480.56100

CAS Registry Number: 88040-23-7
Melting point: 150ºC
Exterior: White or almost white crystalline powder
Application: Respiratory infections, etc.
p H: 4.0-6.0

Introduction to Cefepime Compounds

Cefepime Basic Information

Chinese name: Cefepime

Chinese alias: Cefepime; 1- (6R, 7R) -7- [2- (2-amino-4-thiazolyl) (methoxyimino) acetamide] -2-carboxy-8-oxy-5 -Sulfan-1-azabicyclo [4.2.0] oct-2-en-3-methyl-1-methylpyrrole internal salt; [6R-[(6, 7 (Z)]]-7- [ [(2-amino-4-thiazolyl) (methoxyimino) acetyl] amino] .2-carboxy-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2 -En-3-yl] methyl] -1-methylpyrrolinium ammonium internal salt;

English name: cefepime

English alias: CFPM; 7-[(Z) -2- (2-aminothiazol-4-yl) -2-methoxyiminoacetamido] -3- (1-methylpyrrolidino) methyl-3-cephem-4-carboxylate; (6R, 7R ) -7- [2- (2-amino-4-thiazolyl) -2- (Z)-(methoxyimino) acetamido] -3-[(1-methyl-1-pyrrolidinium) methyl] -3-cephem-4- carboxylate; Tsefepim; Cefepime;

CAS number: 88040-23-7

Molecular formula: C ₁₉ H ₂₄ N ₆ O ₅ S ₂

Molecular weight: 480.56100

Structural formula:

Exact mass: 480.12500

PSA: 203.58000 ^[1]

Cefepime physical and chemical properties

Appearance and properties: white or almost white crystalline powder

Melting point: 150ºC ^[1]

Cefepime calculated chemical data

1. Hydrophobic parameter calculation reference value (XlogP): None

2.Number of hydrogen-bonded donors: 2

3.Number of hydrogen bond acceptors: 10

4.Number of rotatable chemical bonds: 6

5.Number of tautomers: 14

6. Topological molecular polar surface area 204

7.Number of heavy atoms: 32

8.Surface charge: 0

9.Complexity: 869

10.Number of isotope atoms: 0

11. Determine the number of atomic stereocenters: 2

12. Uncertain number of atomic stereocenters: 0

13. Determine the number of chemical bond stereocenters: 1

14. Uncertain number of chemical bond stereocenters: 0

15. Number of covalent bond units: 1 ^[2]

Cefepime uses

Fourth-generation cephalosporins. Its antibacterial spectrum has been further expanded, and it has strong antibacterial activity against a variety of Gram-positive and negative bacteria, including Enterobacter, Pseudomonas aeruginosa and other non-fermentative bacteria, Haemophilus, Staphylococcus, etc. It is used for various infections caused by sensitive bacteria, and is mainly used for respiratory infections such as Staphylococcus aureus, Enterobacter and Pseudomonas aeruginosa. ^[2]

Cefepime production method

1 Cefepime Method 1:

The total yield can reach 25%.

7-Amino-3-chloromethyl-3-cephem-4-carboxylic acid diphenylmethyl ester hydrochloride (I, 50 g, 0.11 mol) was suspended in a mixture of 400 ml of ethyl acetate and 150 ml of water, and With the bath cooled, 200 ml of a 1 mol / L sodium hydroxide solution was added. After the addition was complete, stirring was continued for 30 min to obtain a clear two-phase solution. The ethyl acetate layer was separated. It was washed with 300 ml of water and dried with 100 g of anhydrous sodium sulfate. The ethyl acetate solution (without removing sodium sulfate) was stirred with benzaldehyde (14.2 g, 0.13 mol) at room temperature for 2 h. The insoluble matter (ie, sodium sulfate) was removed by filtration, and the filtrate was concentrated under reduced pressure to about 200 ml, and 400 rnl of n-pentane was added to precipitate out. Collected by filtration to obtain 47.6 g of compound (II) with a yield of 86%. The filtrate was concentrated to about 100 ml, 300 ml of n-pentane was added, and the precipitate was collected by filtration to obtain 4.6 g of compound (II) in a yield of 8%. A total of 52.2 g, yield 94%, pale yellow prismatic crystals, melting point 110-111 ° C.

Compound (II) (52 g, 0.10 rml) was dissolved in 1 L of carbon tetrachloride, and a solution of sodium iodide (18.6 g, 0.12 mo1) in 200 ml of acetone was added dropwise while stirring. After the addition was complete, stirring was continued for 40 min at room temperature. Filtered through Dicalite, and the filtrate was washed with 750 ml of a saturated aqueous sodium thiosulfate solution and an aqueous sodium chloride solution (2 × 700 ml), dried with 100 g of anhydrous sodium sulfate, and filtered. A small portion of the filtrate was concentrated to dryness to obtain compound (III). The compound is unstable at room temperature, can only stand for a few days, and has a purity of 65% (determined by HPLC). Part of the filtrate was directly used in the next reaction without separating compound (III). The filtrate was cooled to 0 ° C, and a solution of N-methylpyrrolidine (11.8 g, 0.11 mol) dissolved in 50 ml of carbon tetrachloride was added dropwise under stirring for 30 min. After stirring at 0 to 5 ° C. for 1 h, the precipitate was collected by filtration, washed with 300 ml of carbon tetrachloride, and dried under vacuum in the presence of phosphorus pentoxide. 70 g of compound (IV) were obtained, and the melting point was 120 ° C (decomposed).

Compound (IV) (68 g, purity 60%), 68 ml of 98% formic acid, and 42 ml of concentrated hydrochloric acid were stirred together at room temperature for 1 h. With vigorous stirring, the reaction solution was poured into 2.5 L of acetone. The formed precipitate was collected by filtration and dried to obtain 30 g of a hygroscopic solid. This solid was dissolved in 300 ml of water, and 1.5 L of acetone was added to crystallize to obtain 13.7 g of the compound (V) as colorless prismatic crystals.

Compound (V) (13.7g, 37mmo1) was dissolved in 140ml of water and 280ml of dimethylformamide. Under cooling and stirring in an ice bath, sodium bicarbonate (6.2g, 74mmo1) was added in portions within 5min to obtain a clear solution. Then, the active ester compound (VI) (17.7 g, 55.5 mmol) was added, and after stirring at room temperature for 1 hour, 5 ml of 2 mol / L was used. Sulfuric acid was acidified to Ph = 3. The insoluble matter was filtered off and washed with 10 ml of water. The filtrate and washing solution were combined, and 3 L of acetone was poured under vigorous stirring to cause precipitation. The precipitate was collected by filtration, and dried to obtain 20.6 g of crude cefepime sulfate with a purity of 85% (HPLC). The crude product was dissolved in 120 ml of water, 40 ml of 2 mol / L sulfuric acid was added, and several pieces of cefpimei sulfate crystals were put in the refrigerator and left in the refrigerator for 2 h. The formed crystalline powder was collected by filtration, and 40 ml of 0.5 mol / L was sequentially used. Wash with sulfuric acid and 200 ml of acetone and dry. 15.0 g of cefepime sulfate was obtained with a yield of 70% and a melting point of 210 ° C (decomposed). ^[1]

2 Cefepime Method 2:

After attaching the side chain at the 7 position, the reaction is performed at the 3 position.

Compound (I) (2.29 g, 5.07 mmo1) was dissolved in 57 ml of acetonitrile, and N, O-bis (trimethylsilyl) acetamide (4.09 g, 16.6 mmo1) was reacted at room temperature for 50 min to obtain a clear solution. Add an acid chloride solution. The acid chloride solution was prepared from (Z) -2-methoxyimino-2- (2-tritylaminothiazol-4-yl) acetic acid (fluorene, 2.04 g, 4.60 mmo1) and phosphorus pentachloride (1.15 g, 5.52 mmo1) in 20 ml of dichloromethane. After the acid chloride solution was added, it was stirred at room temperature for 30 min. Pour into 200 ml of cold water and extract with ethyl acetate (3 x 100 ml). The extracts were combined, washed with an aqueous solution of sodium chloride, dried, and evaporated. The residue (4 g) was subjected to silica gel column chromatography, eluting with 10: 1 and 3: 1 toluene and ethyl acetate in that order. There was obtained 2.61 g of the compound (VII) as an amorphous powder, with a yield of 74% and a melting point of 130 ° C.

Compound (VII) (1.50 g, 1.79 mmo1) and sodium iodide (1.34 g, 8.93 mmo1) in 30 ml of methyl ethyl ketone were stirred at room temperature for 1 h. The solvent was evaporated, and the residue was dissolved in 100 ml of ethyl acetate, washed with water, an aqueous sodium thiosulfate solution and an aqueous sodium chloride solution in this order, dried, and evaporated. 1.47 g of the compound (i) was obtained as an amorphous powder, with a yield of 89% and a melting point of 120 ° C (decomposition).

Starting from compound (VII), there are various methods for obtaining cefpimet. However, these methods all require a complicated HPLC separation process. One of them is introduced as follows:

Compound (VII) (5.0 g, 5.3.7 mmol) was dissolved in 500 ml of ether, N-methylpyrrolidine (915 mg, 11.5 mmol) was added, and the mixture was stirred at room temperature for 1 h. The resulting precipitate was collected by filtration, washed with diethyl ether (2 × 100 ml), and dried under vacuum to obtain 3.38 g of compound (X). After the filtrate was left at room temperature for 1 h, 610 mg of compound (X) was obtained. The total yield is 73%.

3.99 g of compound (X) and 20 ml of 90% trifluoroacetic acid were reacted at room temperature for 1 h. It was evaporated in vacuo and the residue was impregnated with 200 ml of ether to give 3.03 g of a solid. The solid consisted of cefepime and its isomers (2.6: 1). By complicated HPLC separation, 7.573 mg of cefepime was obtained as a colorless powder with a yield of 22% [calculated as compound (VII)]. ^[1]

Cefepime pharmacological effects

1. Cefepime hydrochloride is the fourth-generation cephalosporin. Its antibacterial action mechanism is through binding with one or more penicillin-binding proteins (PBPs) of bacterial cells, which affects the synthesis and metabolism of bacterial cell walls, thereby playing an antibacterial effect. Cefepime's action characteristics are: high antibacterial activity, stable to -lactamase, especially chromosome-mediated Richmond-sykes type -lactamase, and very resistant to Gram-negative bacteria producing type I -lactamase Strong antibacterial activity. Cefepime's antibacterial activity against Enterobacteria, Citrobacter, Serratia producing type I -lactamase is higher than that of third-generation cephalosporins such as ceftazidime; antibacterial against Pseudomonas aeruginosa The effect is similar to or slightly worse than that of ceftazidime; the antibacterial activity against Gram-positive bacteria such as Staphylococcus aureus is also enhanced than that of the third-generation cephalosporins. Cefepime has antibacterial activity against most Gram-positive and Gram-negative bacteria. Its antibacterial spectrum includes: 1. Gram-positive aerobic bacteria: Staphylococcus aureus (including -lactamase producing strains), Staphylococcus epidermidis (including -lactamase producing strains), Streptococcus pyogenes, and dairy-free Streptococcus, Streptococcus pneumoniae and other hemolytic streptococci, Streptococcus bovis, Streptococcus grass green.

2. Gram-negative aerobic bacteria: Pseudomonas (including Pseudomonas aeruginosa, Pseudomonas putida), Escherichia coli, Klebsiella, Enterobacter (including Enterobacter cloacae, gas producing Enterobacter), mutants (including Proteus mirabilis, Proteus mirabilis), citrate, Campylobacter jejuni, Haemophilus duquei, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae Neisseria gonorrhoeae, Neisseria meningitidis, Salmonella, Serratia, Shigella, Yersinia enterocolitica.

3. Anaerobic bacteria: Bacteroides, Clostridium perfringens, Clostridium, Streptococcus, Veillonella. Cefepime hydrochloride has no antibacterial activity against most enterococci (such as Enterococcus faecalis, methicillin-resistant Staphylococcus), Pseudomonas maltophilus, Bacteroides fragile, and Clostridium difficile. ^[3]

Cefepime Toxicology

Genotoxicity: The results of internal and external studies have not found that the product is genotoxic.

Reproductive toxicity: mice, rats and rabbits were given doses of 1200, 1000, and 100 mg / kg (in terms of surface area in vitro, respectively equivalent to 1-4 times the maximum recommended clinical dose for humans). Have a significant impact on animal fertility and reproduction. However, there are no sufficient and rigorous research data on pregnant women, and the correlation between animals and humans is unclear. ^[3]

Cefepime pharmacokinetics

Cefepime Cefepime is rapidly absorbed after intravenous or intramuscular administration, with an absolute bioavailability of 100%. Intravenous injection of 2.0 g of the drug resulted in a peak blood concentration of approximately 193 g / ml. The drug is widely distributed after absorption and can reach effective antibacterial concentrations in urine, bile, peritoneal fluid, tracheal mucosa, sputum, prostate fluid, appendix and gallbladder. The steady-state volume of cefepime is about 20L / kg, and it is not related to the dose. Cefepime blood plasma protein binding rate is about 20%. After a single dose of intramuscular or intravenous injection of 250 to 2000 mg, the average plasma clearance half-life is 2.0 hours. The clearance half-life of patients with renal insufficiency is prolonged. The pharmacokinetics of patients with liver dysfunction are unchanged. The average half-life of patients requiring dialysis is 13 hours. The half-life of continuous peritoneal dialysis was 19h. The overall clearance rate of cefepime is 120-130 ml per minute, of which about 85% of the drug is excreted in the urine through the kidney. Healthy subjects received 2 g intravenously every 8 hours. No drug accumulation was observed for 9 consecutive days. ^[3]

Cefepime indications

Cefepime Cefepime is used to treat the following infections caused by sensitive bacteria:

1. Lower respiratory tract infections, such as pneumonia and bronchitis.

2. Urinary system infections, such as pyelonephritis.

3. Skin and soft tissue infections.

4. Abdominal infections (including peritonitis and biliary infections, etc.).

5. Obstetrics and Gynecology Infection.

6. Septicemia.

7. Cefepime can be used for empirical treatment of patients with neutropenic fever. ^[3]

Cefepime usage dosage

1. Intramuscular injection: 1g each time, 2 times a day, deep intramuscular injection, the course of treatment is 7 to 10 days. Severe infection 2 g each time, 2 to 3 times a day.

2. Intravenous administration: 1g each time, 2 times a day for 7 to 10 days. Severe infection 2 g each time, 2 to 3 times a day, dissolved in 100 ml of physiological saline intravenously. ^[3]

Cefepime adverse reactions

The adverse reactions were few and mild. 8% 14% of the adverse reactions occurred in 2834 cases. Mainly diarrhea (2.1%), headache (1.7%), rash (1.6%), nausea (1.4%), vomiting (0.9%) and pruritus, constipation, dizziness, etc., 2% of patients who need to stop taking medicine due to reactions . Occasionally fever, oral and vaginal Candida infection, pseudomembranous enteritis, local pain or phlebitis. ^[3]

Cefepime contraindications

1. Those who are allergic to cefepime or other cephalosporins are prohibited.

2. Those with high sensitivity to L-arginine, penicillin drugs or other -lactam antibiotics are contraindicated. ^[3]

Cefepime precautions

1. Cross-allergy: People who are allergic to one cephalosporin may also be allergic to other cephalosporins; people who are allergic to penicillins, penicillin derivatives or penicillamine may also be allergic to cephalosporins.

2. Use with caution: (1) pregnant and lactating women; (2) those with renal insufficiency; (3) those with a history of gastrointestinal diseases, especially those with ulcerative colitis, localized enteritis or pseudomembranous enteritis; (4) Children under 13 years of age.

3. The effect of the drug on the test value or diagnosis: (1) during the use of cefepime, the direct anti-human globulin (Coombs) test showed a positive response; (2) the urine glucose measurement using a reagent containing copper sulfate, which may be false Positive. ^[3]

Cefepime administered during pregnancy

Although animal reproductive toxicity tests and teratogenicity tests show that cefepime is not teratogenic and embryotoxic, there are no sufficient and well-controlled clinical data of this product for pregnant women and women during childbirth. Therefore, this product should be used with caution in pregnant women.

Cefepime is excreted in a very small amount in human milk (concentration of about 0.5 & micro; g / ml). Cefepime should be used with caution in lactating women.

Cefepime for the elderly

Elderly patients with normal renal function generally use the recommended dosage, and its efficacy and safety are similar to other adult patients; elderly patients with renal insufficiency should use this product, and the dosing plan should be adjusted according to renal function. ^[3]

Cefepime 's interaction with other drugs

1. Cefepime and aminoglycosides (such as gentamicin or amikacin) have a synergistic antibacterial effect; but when combined, they can increase renal toxicity.

2. Cefepime can increase renal toxicity when used with strong diuretics.

3. The combined use of cefepime and typhoid vaccine will reduce the immune effect of typhoid vaccine. The possible mechanism is that cefepime has antibacterial activity against Salmonella typhimurium. ^[3]

Cefepime overdose

Patients with overdose should carefully observe and use supportive therapy, and use hemodialysis treatment to promote drug elimination, and peritoneal dialysis should not be used. Within 3 hours of the beginning of hemodialysis, 68% of cefepime in the body can be excreted. ^[3]

Cefepime Expert Review

Cefepime is a new fourth-generation cephalosporin, which is effective against many Gram-positive and Gram-negative bacteria including Enterobacteria, Pseudomonas aeruginosa and other non-fermentative Gram-negative bacteria, Haemophilus, Neisser Coccus, Staphylococcus and Streptococcus all have strong antibacterial activity. Cefepime is effective in treating respiratory, urinary, skin and soft tissue, bone and joint, and obstetric and gynecological infections caused by sensitive bacteria. The efficacy is similar to ceftazidime. The effective rate for treating lower respiratory infections is 62% to 90%. Bacteriology The clearance rate is 69% to 97%, and the effective rate for complicated urinary system infection is 72% to 89%. The effect on intraperitoneal infection is similar to that of piperacillin or meloxicillin. According to foreign reports, after the application of cefepime to 112 patients with senile respiratory infections with an average age of 62 years, 93% of the pathogens causing pneumonia and 90% of the bronchitis causing pathogens were removed. In 112 clinical isolates, the most common It is pneumococcus, Haemophilus influenzae, Pseudomonas aeruginosa or Staphylococcus aureus. In addition, 31 patients with acquired respiratory infections in the elderly were reportedly instilled with 2 g each time, 2 times a day for 7 to 14 consecutive days. The results showed that the cure rate, effective rate, and bacterial clearance rate were 51.6%, 77.4%, and 69.2. %, The adverse reactions were few and slight, the incidence was 6.5%. Another research application, cefepime 2 g each time, 173 cases of severe bacterial infections (55 cases of urinary tract infections, 81 cases of sepsis, 15 other infections), with an effective rate of 80% and a pathogen clearance rate of 85% . In the treatment of 51 patients with nosocomial acquired lower respiratory tract infection, the effective rate was 96% for 1 g twice daily, and the clearance rate for the isolated 73 pathogenic bacteria was 98%. Cefepime has a broad antibacterial spectrum, strong antibacterial activity, precise clinical efficacy, good safety and tolerability, and can be used as an ideal single-empirical treatment for pneumonia in elderly hospitals. ^[3]

Foreground application of cefepime

Anti-infective drugs are indispensable in outpatient and ward medications, and cephalosporins are the main force in antibiotics. This class of drugs not only fully inherits the excellent quality of penicillin, but also has low toxicity and side effects. Favors for doctors and patients. Since the first three generations of cephalosporins have been adjusted in price and profits have fallen, many new drugs have gradually entered the clinic. A new generation of cephalosporins, such as cefepime, cefpirome, cefothiri, and pyrazolidlan, came into being, thus unveiling The prelude to the fourth generation of cephalosporins.

National Basic Medical Insurance and Work Injury Insurance Drug Catalogue Cefepime is one of the 200 best-selling drugs that have entered the sample hospitals of key cities in China in the past two years. It is also the fourth-generation cephalosporin among the top 48 anti-infective drugs. Clinical studies have shown that the fourth-generation cephalosporins, while maintaining the characteristics of the third-generation cephalosporins, enhance the antibacterial activity against gram-negative bacteria and improve the stability of -lactamase at lower concentrations. Inhibits bacterial cell wall synthesis and maintains strong antibacterial activity.

Cefepime Cefepime is the fourth-generation cephalosporin developed by Bristol-Myers Squibb. It was first used in clinical practice in Sweden in 1993, and subsequently marketed in Europe, the United States, and Japan. In 1996, cefepime of two pharmaceutical companies, Dura and Elan, was also approved by the US FDA. Subsequently, Bristol-Myers Squibb first introduced cefepime for injection (trade name "Maxipime", Maxipime) in China in 1998, and obtained pharmaceutical administrative protection in China in August 1999. After Maspin was listed in China, he focused on the high-end market and quickly launched the hospital terminal. Because the drug is stable to -lactamase, it has a broader antibacterial spectrum than the current clinically used antibiotic drugs. It has played a good role in the clinical treatment of lower respiratory tract, skin and bone tissue, urinary system, gynecological and abdominal infections caused by sensitive bacteria.

Maspin set a sales record of 264,200 units in a typical city sample hospital in 2001, with a drug amount of 33.71 million yuan. After the Sino-US Shanghai Bristol-Myers joint venture product entered the domestic market in 2002, Maspin's sales volume in the sample hospital increased by 22.18%. The share of imports and joint venture products reached 40.07 million yuan. In 2003, the drug purchase amount in sample hospitals in key cities in the country reached 47.81 million yuan, ranking 78th. In 2004, Maspin's usage in sample cities of key cities has reached 480,000. Under the situation that the country s supervision of antibiotics and drugs is continuously strengthened and prices are continuously adjusted, it is a typical city sample hospital for the domestic pharmaceutical market s barometer. Changes are also taking place, mainly reflected in the slowdown in the increase in the amount of antibiotics used, and the decline in the amount of drugs used to accelerate. However, from the statistical data, Maspin's consumption in 2005 has been slightly better than the previous year. Its sales in the sample hospitals reached 72.938 million yuan, and the consumption exceeded 640,000. Moreover, the market development of domestic cefepime also thrives like a bamboo shoot.

With the expiration of Maspin's product patent US4910301, on September 27, 2000, the administrative protection of this product in China also came to an end. Sino-American Shanghai Bristol-Myers Squibb first developed cefepime. In August 2002, it obtained a new drug certificate and production approval from the State Food and Drug Administration (SFDA), and was marketed in China as four types of new drugs.

National Basic Medical Insurance and Work Injury Insurance Drug Catalogue With the acceleration of the domestic production of 7-ACA for cephalosporin upstream products and the completion of GMP certification for domestic manufacturers, the overcapacity of preparations has exposed the tip of the iceberg, which has led to many manufacturers and R & D institutions. Aimed at the imitation approval market. Since 2003, the fourth-generation cephalosporin research climax has started in China. The main varieties include cefepime, ceftioline, cefpirome, cefazolin, and other APIs and preparations. As of July 2006, SFDA has issued more than 200 production approvals for the first three varieties. At present, cefepime injection has been listed in the September 2004 edition of the "National Basic Medical Insurance and Work Injury Insurance Drug Catalog" as a Class B drug.

It is reported that currently the SFDA has accepted nearly a hundred cefepime application numbers. In November 2004, Shenzhen Xinlitai Pharmaceutical's cefepime drug and powder injections were approved for marketing under the trade name "Xinliwei" and opened. The curtain of this breed competition. So far, the SFDA has issued 14 approvals for cefepime APIs, and in May 2006 approved the production of cefepime hydrochloride / L-arginine by Shenzhen Xinlitai Pharmaceutical. Eighteen companies, including China and the United States Shanghai Bristol-Myers Squibb, North China Pharmaceutical Group Caritas Pharmaceuticals, Guangzhou Baiyunshan Tianxin Pharmaceutical Co., Ltd., have currently held 33 powder injection production approvals.

Under the direct influence of many policies such as strengthening the management of antibiotic prescriptions, preventing the abuse of antibiotics, and lowering the price of antibiotics, the fourth-generation antibiotics have entered a downturn, and the development trend of the high-end market in 2005 has become apparent. However, the amount of cefepime used in the sample hospitals in typical cities in China still reached 72.9381 million yuan. Looking at the product trend throughout the year, the third quarter is still the low period of antibiotics, and the fourth quarter has become inevitable due to seasonal factors. The amount of medication used throughout the year was nearly 100 million yuan, accounting for 3.4% of cephalosporin medication.

The eight major brands of cefepime that entered the sample hospitals in 2005 were Maspin, Caroxin, Yuekang Kaixin, Kangliwopu, Xinliwei, Ruoneng, Danileng, and Boshuai. The share of drug use in the first three quarters showed that the original research drug Maspin occupied 80%, and the other seven brands accounted for 20%. They were Beijing Yuekang Pharmaceutical, North China Pharmaceutical Group Karite Pharmaceutical, Guangzhou Baiyunshan Tianxin Pharmaceutical Co., Ltd., Products of Shenzhen Xinlitai Pharmaceutical Co., Ltd., Harbin Pharmaceutical Group General Factory, Shenzhen Pharmaceutical Factory, Hainan Star Pharmaceutical Co., Ltd.

At present, cefepime has certain advantages from clinical efficacy to price, which has become a highly competitive variety in the market, but the statistical price of the original research drug in the pharmacy is still the highest. The powder injection of 1000mg specifications has the largest difference compared with domestic drugs. 192%, while 500mg powder (Elan) powder injections differ by up to 151% compared with domestic medicines, while the price of domestic medicines is relatively low.

Among the domestic cephalosporin manufacturers of Harbin Pharmaceutical Group, the top 10 companies in 2005 were: Harbin Pharmaceutical Group General Factory, Guangzhou Tianxin Pharmaceutical and Baiyunshan Pharmaceutical General Factory under Shanghai Pharmaceutical Group, Shanghai Roche, Pfizer The top ten pharmaceutical companies, Livzon Group, Shanghai Bristol-Myers Squibb, Shenzhen Pharmaceutical Factory, Shanghai Pioneer Pharmaceuticals, Hainan Hailing Pharmaceutical already accounted for 42.35% of cephalosporin medications in sample hospitals across the country.

In order to avoid the fight for the price of antibiotic APIs, domestic companies have shifted their targets to specialty APIs in an attempt to occupy the market through differentiated product strategies, although their sales volume is limited, but their profits are high. At present, there are nearly 20 varieties of -lactam-type APIs listed in China.

Although there are already 15 cefepime bulk drug production approvals in China, the production capacity of cefepime aseptic powder in China is not mature enough, and the production capacity needs to be improved urgently in a considerable period of time, and the production process needs to be further optimized. Some companies have not fully completed the transformation of product results. The cefepime raw materials on the market are mainly provided by China Pharmaceutical Group Aojide Pharmaceutical and Shenzhen Xinlitai Pharmaceutical.

It is understood that Orchide Pharmaceuticals, a cefepime drug substance, is an antibiotic aseptic drug substance company established by North China Pharmaceuticals and Indian Orchid. The company has introduced the mature technology and foreign equipment of Cephalosporin raw materials produced by Indian Orchid Company. After the introduction of a new cefepime variety in 2005, it led to a trend for the cefepime market to go wild.

From the market information feedback in the first half of 2005, the price of domestic cefepime + arginine has not changed much. The price of the product has remained relatively stable from June to early August, and the price has remained at 6,800 yuan / kg, an increase of only 4% over the beginning of the year. The price has dropped by 43% compared to the initial offer.

According to China Health Net, in the first half of 2005, China imported only 1270 kilograms of cefepime hydrochloride / L-arginine from Bristol-Myers Squibb in Italy, and the annual demand was about 3 tons. Because the product is relatively new in China and the profit of the preparation product is relatively high, companies are paying more attention to these relatively competitive products when looking for new profit growth points. The current imported cefepime raw materials are mainly derived from Alembiclimited in India. And Orchid Chemicals, the two imported cefepime raw materials are mainly used for joint ventures to produce formulations. Although the price of cefepime API decreased in early 2006, according to the market price of cefepime (CP / BP / USP) in Zhejiang from January to April, the price of ordinary non-sterile APIs was 5,000 yuan / kg, while that of aseptic The medicine is about 6000 yuan / kg.

In short, in recent years, there are more broad-spectrum cephalosporins on the market, but the antibacterial spectrum is unbalanced. Each generation has its own unique mechanism. Cefepime is the first fourth-generation cephalosporin drug listed in China. It has a wide range of applications, good antibacterial activity and small side effects, and has become a market-leading product with a highly balanced mechanism of action in the antibacterial spectrum.