Cefalotin

Structural formula
General
Non-proprietary name	Cefalotin
other names	(6 R , 7 R ) -3- (acetoxymethyl) -8-oxo-7- [2- (thiophen-2-yl) acetamido] -5-thia-1-azabicyclo [4.2.0] oct-2-en -2-carboxylic acid ( IUPAC ) Cefalotinum ( Latin )
Molecular formula	C 16 H 16 N 2 O 6 S 2 C 16 H 15 NaN 2 O 6 S 2 (sodium salt)
External identifiers / databases
CAS number 153-61-7 58-71-9 (cefalotin sodium) EC number 205-815-7 ECHA InfoCard 100.005.288 PubChem 6024 ChemSpider 5802 DrugBank DB00456 Wikidata Q2736126
Drug information
ATC code	J01 DB03
Drug class	β-lactam antibiotic 1st generation cephalosporins
Mechanism of action	Transpeptidase inhibitors
properties
Molar mass	396.44 g · mol -1
Physical state	firmly
Melting point	160-160.5 ° C
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances Cefalotin sodium danger H and P phrases H: 317-334 P: 261-280-284-304 + 340-342 + 311
Toxicological data	2200 mg kg −1 ( LD 50 ,  mouse ,  iv )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Cefalotin is an antibiotic used to treat severe infections of the blood, bones, joints, airways, skin, and urinary tract, and to prevent infections during certain operations. It is produced semisynthetically and comes from the class of the cephalosporins of the 1st generation. Cefalotin was patented by Eli Lilly in 1962 and was the first cephalosporin to be marketed. It was launched in the USA in 1963 as Keflin , but it is no longer approved. There are no finished medicinal products in Germany either.

indication

Since, among the cephalosporins, cefalotin is particularly effective against severe staphylococcal infections, it is mostly used here. These include, for example, respiratory infections, skin and soft tissue infections (including peritonitis ), infections of the urogenital tract , septicemia (including endocarditis ) and infections of the bones and joints caused by sensitive germs. Prophylactic cefalotin can be indicated for vaginal hysterectomy , head and neck surgery , insertion of heart valve replacements and endoprostheses .

Working principle and metabolism

The cefalotin molecules bind - like all cephalosporins - to specific penicillin-binding proteins , which are required for the reconstruction of the bacterial cell wall. This prevents further synthesis of the bacterial cell wall.

In the body, around half of the cefalotin ingested is converted to the less active metabolite O -desacetylcefalotin through deacetylation . The other half is eliminated unchanged in the urine. The plasma half-life is - with normal kidney function - around 50 minutes.

Microbiological spectrum of activity

In general, cefalotin has a higher activity against gram-positive than against gram-negative bacteria, the latter varying in their sensitivity - depending on the isolate - to the substance. In vitro , for example, cefalotin is effective against beta-hemolytic and other streptococci (on the other hand enterococci such as Streptococcus faecalis are resistant ), staphylococci (including coagulase-positive and coagulase-negative and penicillinase- producing strains; however , methicillin-resistant streptococci are not susceptible to pneumoniae , streptococci ) Haemophilus influenza , Escherichia coli , Klebsiella , and Proteus mirabilis . Like other indole-producing proteobacteria,
pseudomonads are resistant to cefalotin.

Application

Cefalotin sodium, a white to almost white powder that is easily soluble in water and sparingly soluble in anhydrous ethanol, is used medicinally. The salt having the empirical formula C ₁₆ H ₁₅ N ₂ NaO ₆ S ₂ has a molecular weight of 418.43 g · mol ^-1 , and melts at 204-205 ° C .

The drug is administered parenterally .

Ready-to-use reconstituted solutions are stable for twelve hours at room temperature and 96 hours in the refrigerator. However, the activity decreases sharply, so that after three days it is only 80%. The manufacturer describes the effectiveness as sufficient after a maximum of 48 hours of storage in the refrigerator.

synthesis

The synthesis of cefalotin takes place via a semisynthesis , which in this case means the acylation of an amino group . The 7-aminocephalosporanic acid (7-ACA for short) to be acylated is converted from penicillin G with the help of N , N ′ -bis (trimethylsilyl) urea through a chemical reaction .

Thereafter, the reaction of 7-ACA ( 2 ) with thiophenylacetyl chloride ( 1 ) in acetone forms cefalotin ( 3 ).

Synthesis of cefalotin from 7-ACA and thiophenylacetyl chloride

Individual evidence

1. ↑ ^{a b c d} Entry on cefalotin. In: Römpp Online . Georg Thieme Verlag, accessed on March 13, 2019.
2. ↑ ^{a b} Data sheet Cefalotin sodium from Sigma-Aldrich , accessed on May 22, 2019 ( PDF ).
3. ↑ Drug and Therapeutics Bulletin; London vol. 7, ed. 26, (Dec 1969): 101. doi: 10.1136 / dtb.7.26.101.
4. ^ David Greenwood: Antimicrobial Drugs: Chronicle of a Twentieth Century Medical Triumph . OUP Oxford, 2008, ISBN 978-0-19-953484-5 , pp. 128 ff . ( google.de [accessed on May 8, 2019]).
5. ↑ Drug Update: Fluoroquinolones. German STI Society - Society for the Promotion of Sexual Health, accessed on May 17, 2019 . 
6. ↑ ^{a b c d} Product Information KEFLIN . Aspen Pharmacare Australia Pty Ltd. As of October 2008. Accessed May 24, 2019.
7. ↑ Mutschler, Ernst .: drug effects: textbook of pharmacology and toxicology: with introductory chapters in anatomy, physiology and pathophysiology . 5., completely reworked and adult. Aufl. Wissenschaftliche Verlagsgesellschaft, Stuttgart 1986, ISBN 978-3-8047-0839-6 .
8. ↑ ^{a b} Entry on cefalotin in the DrugBank of the University of Alberta , accessed May 22, 2019.
9. ↑ External identifiers of or database links for cefalotin sodium, IUPAC name: sodium [(6 R , 7 R ) -3 - [(acetyloxy) methyl] -8-oxo-7 - [(thiophen-2-ylacetyl ) amino] -5-thia-1-azabicyclo [4.2.0] oct-2-en-2-carboxylate] : CAS number: 58-71-9, EC number: 200-394-6, ECHA -InfoCard : 100.000.358 , PubChem : 23675321 , ChemSpider : 5801 , DrugBank : DB00456 , Wikidata : Q27106126 .
10. ↑ European Pharmacopoeia Commission (ed.): European Pharmacopoeia, 9th edition, basic work 2017. Monograph: Cefalotin sodium .
11. ↑ Entry on cefalotin at Vetpharm, accessed on May 22, 2019.
12. ↑ Alle Bruggink (Ed.): Synthesis of β-Lactam Antibiotics: Chemistry, Biocatalysis & Process Integration. Springer Science + Business Media, ISBN 978-0-7923-7060-4 , p. 15 .
13. ↑ Entry on CEPHALORIDINE in the Hazardous Substances Data Bank , accessed on May 27, 2019.

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !