Misplaced Pages

Cefquinome: Difference between revisions

Article snapshot taken from Wikipedia with creative commons attribution-sharealike license. Give it a read and then ask your questions in the chat. We can research this topic together.
Browse history interactively
Page 1
Page 2
← Previous editContent deleted Content addedVisualWikitext
Revision as of 14:07, 7 August 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'StdInChI', 'StdInChIKey').← Previous edit Latest revision as of 20:53, 10 October 2024 edit undoJWBE (talk | contribs)Extended confirmed users10,126 edits removed Category:Ketoximes; added Category:Ketoxime ethers using HotCat 
(54 intermediate revisions by 36 users not shown)
Line 1: Line 1:
{{cs1 config|name-list-style=vanc}}
{{short description|Chemical compound}}
{{refimprove|date=March 2014}}
{{drugbox {{drugbox
| Watchedfields = changed
| verifiedrevid = 443511465
| UNII_Ref = {{fdacite|correct|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = Z74S078CWP | UNII = Z74S078CWP
| IUPAC_name = 1-<nowiki>amino]-2-carboxy-8-oxo-<br />5-thia-1-azabicyclomethyl]-<br />5,6,7,8-tetrahydroquinolinium inner salt | IUPAC_name = 1-<nowiki>amino]-2-carboxy-8-oxo-5-thia-1-azabicyclomethyl]-5,6,7,8-tetrahydroquinolinium inner salt
| image = Cefquinome.svg | image = Cefquinome.svg
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 16736863 | ChemSpiderID = 16736863
| InChI = 1/C23H24N6O5S2/c1-34-27-16(14-11-36-23(24)25-14)19(30)26-17-20(31)29-18(22(32)33)13(10-35-21(17)29)9-28-8-4-6-12-5-2-3-7-15(12)28/h4,6,8,11,17,21H,2-3,5,7,9-10H2,1H3,(H3-,24,25,26,30,32,33)/b27-16+/t17-,21-/m1/s1
| smiles = O=C4(NC(=O)C(=N\OC)/c1csc(N)n1)5SC\C(C3cccc2CCCCc23)=C(/N45)C()=O | smiles = O=C4(NC(=O)C(=N\OC)/c1csc(N)n1)5SC\C(C3cccc2CCCCc23)=C(/N45)C()=O
| CAS_number_Ref = {{cascite|correct|??}}
| InChIKey = YWKJNRNSJKEFMK-KJXIDEHUBC
| InChI1 = 1/C23H24N6O5S2/c1-34-27-16(14-11-36-23(24)25-14)19(30)26-17-20(31)29-18(22(32)33)13(10-35-21(17)29)9-28-8-4-6-12-5-2-3-7-15(12)28/h4,6,8,11,17,21H,2-3,5,7,9-10H2,1H3,(H3-,24,25,26,30,32,33)/b27-16-/t17-,21-/m1/s1
| CAS_number = 84957-30-2 | CAS_number = 84957-30-2
| ChEMBL = 2103931
| ATCvet = yes | ATCvet = yes
| ATC_prefix = J01 | ATC_prefix = G51
| ATC_suffix = DE90 | ATC_suffix = AA07
| ATC_supplemental = {{ATCvet|J51|DA92}} | ATC_supplemental = {{ATCvet|J01|DE90}} {{ATCvet|J51|DE90}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C23H24N6O5S2/c1-34-27-16(14-11-36-23(24)25-14)19(30)26-17-20(31)29-18(22(32)33)13(10-35-21(17)29)9-28-8-4-6-12-5-2-3-7-15(12)28/h4,6,8,11,17,21H,2-3,5,7,9-10H2,1H3,(H3-,24,25,26,30,32,33)/b27-16-/t17-,21-/m1/s1 | StdInChI = 1S/C23H24N6O5S2/c1-34-27-16(14-11-36-23(24)25-14)19(30)26-17-20(31)29-18(22(32)33)13(10-35-21(17)29)9-28-8-4-6-12-5-2-3-7-15(12)28/h4,6,8,11,17,21H,2-3,5,7,9-10H2,1H3,(H3-,24,25,26,30,32,33)/b27-16-/t17-,21-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = YWKJNRNSJKEFMK-PQFQYKRASA-N | StdInChIKey = YWKJNRNSJKEFMK-PQFQYKRASA-N
| PubChem = | PubChem =
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = | DrugBank =
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07652 | KEGG = D07652
| C = 23 | H = 24 | N = 6 | O = 5 | S = 2 | C=23 | H=24 | N=6 | O=5 | S=2
| molecular_weight = 528.60 g/mol
| bioavailability = 87% | bioavailability = 87%
| protein_bound = <5% | protein_bound = <5%
Line 31: Line 39:
| legal_AU = <!-- Unscheduled / S2 / S4 / S8 --> | legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->
| legal_UK = <!-- GSL / P / POM / CD --> | legal_UK = <!-- GSL / P / POM / CD -->
| legal_US = Rx-only, Unscheduled | legal_US = Unscheduled
| legal_US_comment = Rx-only
| legal_status = | legal_status =
| routes_of_administration = | routes_of_administration =
}} }}

'''Cefquinome''' is a fourth generation ] with pharmacological and antibacterial properties valuable in the treatment of coliform mastitis and other infections. It is only used in veterinary applications. '''Cefquinome''' is a fourth-generation ] with pharmacological and antibacterial properties valuable in the treatment of coliform mastitis and other infections. It is only used in veterinary applications.


== Properties == == Properties ==
Cefquinome is resistant to ]. Chemically, its ] structure can facilitate rapid penetration across biological membranes, including ] of bacterial cell wall. Plus, it has a higher affinity to target penicillin binding proteins. The reactive site is a ] nucleus, while the main peripheral functional groups are a quaternary quinolinium, an aminothiazolyl moiety and an unusual ''O''-alkylated ]. Cefquinome is resistant to ]. Chemically, its ]ic structure can facilitate rapid penetration across biological membranes, including ] of bacterial cell walls. Plus, it has a higher affinity to target penicillin-binding proteins. The reactive site is a ] nucleus, while the main peripheral functional groups are a quaternary quinolinium, an {{chem name|aminothiazolyl}} moiety and an unusual ''O''-alkylated ].


Cefquinome acts by inhibition of the cell wall synthesis, but it has a relatively short half-life of about two and half hours. It is less than 5% protein bound and is excreted unchanged in the urine.<ref name="Intervet">Intervet, "Cephaguard Injection Data Sheet," http://www.intervet.co.uk/Products_Public/Cephaguard_Injection/090_Product_Datasheet.asp</ref> Cefquinome acts by inhibition of the cell wall synthesis, but it has a relatively short half-life of about 2.5 hours. It is less than 5% protein bound and is excreted unchanged in the urine.<ref name="Intervet">Intervet, "Cephaguard Injection Data Sheet," {{cite web |url=http://www.intervet.co.uk/Products_Public/Cephaguard_Injection/090_Product_Datasheet.asp |title=Cephaguard Injection - Product Datasheet |access-date=2007-04-27 |url-status=dead |archive-url=https://web.archive.org/web/20050115193430/http://www.intervet.co.uk/Products_Public/Cephaguard_Injection/090_Product_Datasheet.asp |archive-date= 15 January 2005 }}</ref>


== Studies == == Studies ==


Many studies have been conducted, mostly for animal use. One such study was conducted by the Pharma Research in Germany. Many studies have been conducted, mostly for animal use. One such study was conducted by the Pharma Research in Germany.


=== Test groups === === Test groups ===
Groups of albino mice, weighing 191 g, were dosed with 10 and 40&nbsp;mg of cefquinome per kg. Blood samples were obtained from a cut at the tip of the tail and kept at 4 degrees Celsius. Urine was collected in metabolism cages. Groups of albino mice, weighing 191&nbsp;g, were dosed with 10 and 40&nbsp;mg of cefquinome per kg. Blood samples were obtained from a cut at the tip of the tail and kept at 4°C. Urine was collected in metabolism cages.


Three male beagle dogs, weighing about 22&nbsp;kg each, were dosed with 5, 10, and 20&nbsp;mg/kg at the ]. Blood samples were drawn from the same vein in the opposite leg. Meanwhile, urine was collected by catheterization. Three male beagle dogs, weighing about 22&nbsp;kg each, were dosed with 5, 10, and 20&nbsp;mg/kg at the ]. Blood samples were drawn from the same vein in the opposite leg. Meanwhile, urine was collected by catheterization.


Pigs, five or six male and female in each group weighing approximately 18&nbsp;kg each, were injected with 10&nbsp;mg of cefquinome at the venajuglaris in the base of the left ear. Blood samples were withdrawn from the contralateral jugular vein. Pigs, five or six male and female in each group weighing about 18&nbsp;kg each, were injected with 10&nbsp;mg of cefquinome at the '']'' in the base of the left ear. Blood samples were withdrawn from the contralateral jugular vein.


Male and female calves were weighing between 110 and 140&nbsp;kg were dosed with 10&nbsp;mg of cefquinome per kg through the vera jucular. Male and female calves weighing between 110 and 140&nbsp;kg were dosed with 10&nbsp;mg of cefquinome per kg through the ''vena jugularis''.


Standard solutions were prepared from pooled murine blood and urine taken from untreated dogs, pigs, and calves. Standard solutions were prepared from pooled murine blood and urine taken from untreated dogs, pigs, and calves.


=== Calculations === === Calculations ===
Cefquinome concentrations were calculated by regression analysis, using the standard curves in which logarithms of the concentration were proportional to the areas of the inhibition zones. ] was carried out by nonlinear regression with the computer program PHAKOK. Pharmokinetic analysis of the concentration-time data after administration indicated that the best curve fits were usually achieved by using an open two-compartment model. Cefquinome concentrations were calculated by regression analysis, using the standard curves in which logarithms of the concentration were proportional to the areas of the inhibition zones. ] was carried out by nonlinear regression with the computer program PHAKOK. Pharmacokinetic analysis of the concentration-time data after administration indicated that the best curve fits were usually achieved by using an open two-compartment model.


=== Conclusion === === Conclusion ===
Data indicate that cefquinome has high antibacterial activity in vitro against nearly all strains tested. In general, cefquinome is within the same range as cefpirome and ]. Against gram-negative species, cefquinome has very limited in vitro activity. The in vitro activity of cefquinome does not depend on the composition or pH of the test medium. The broad antibacterial spectrum and the high in vitro activity are reflected by high in vivo efficacy in experimental infections. In mouse models of septicemia, cefquinome possessed high therapetic efficacy. All infections were cured. Data indicate that cefquinome has high antibacterial activity ''in vitro'' against nearly all strains tested. In general, cefquinome is within the same range as cefpirome and ]. Against Gram-negative species, cefquinome has very limited '']'' activity. The ''in vitro'' activity of cefquinome does not depend on the composition or pH of the test medium. The broad antibacterial spectrum and the high ''in vitro'' activity are reflected by high '']'' efficacy in experimental infections. In mouse models of septicaemia, cefquinome possessed high therapeutic efficacy. All infections were cured.


== Intervet == == Intervet ==
] developed cefquinome (Cobactan) to treat bovine respiratory disease, the most common disease in cattle.<ref name="FDA override">Rick Weiss, , ''The Washington Post,'' March 4, 2007, sec. A01</ref> An injection, containing 25&nbsp;mg cefquinome per ml, is given to cattle and pigs. ] developed cefquinome (Cobactan) to treat ], the most common disease in cattle.<ref name="FDA override">{{cite news | vauthors = Weiss R | title = FDA rules override warnings about drug | newspaper = The Washington Post | date = 4 March 2007 | url = https://www.washingtonpost.com/wp-dyn/content/article/2007/03/03/AR2007030301311.html }}</ref> An injection, containing 25&nbsp;mg cefquinome per ml, is given to cattle and pigs.


=== Treatment === === Treatment ===
In cattle, the injection should help against respiratory disease caused by Mannheimia haemolytica and ]. It also helps with acute E. coli mastitis, ], infectious ulbar necrosis, and interdigital necrobacillosis (which is foul in the foot). In calves, it is E. coli septicaemia. In cattle, the injection should help against respiratory disease caused by ''Mannheimia haemolytica'' and '']''. It also helps with acute ''E. coli'' mastitis, ], infectious bulbar necrosis, and interdigital necrobacillosis. In calves, it is effective against ''E. coli'' septicaemia.


For pigs, it would treat the bacterial infections of the lungs and respiratory tract caused by ], Haemophilus parasuis, Actinobacillus pleuropneumoniae, and Streptococcus suis. Mastitis-Metritis-Agalactia Syndrome (MMA) involved with E. coli, ], ], and other cefquinome-sensitive organisms will also be treated. In piglets, the mortality rate in cases of meningitis caused by Streptococcus suis is reduced. It is used in the treatment of mild or moderate lesions caused by Staphylococcus hyicus and arthritis caused by Streptococcus spp. and E. coli. For pigs, it is used to treat bacterial infections of the lungs and respiratory tract caused by '']'', '']'', '']'', and '']''. ] involved with ''E. coli'', '']'', '']'', and other cefquinome-sensitive organisms are also treated. In piglets, the mortality rate in cases of meningitis caused by ''Streptococcus suis'' is reduced. It is used in the treatment of mild or moderate lesions caused by '']'' and arthritis caused by ''Streptococcus'' spp. and ''E. coli''.


=== Usage === <!-- how-to – not encyclopedic === Usage ===
Shake the vial well before using. Shake the vial well before using.


Swab the septum before removing each dose. Use a dry sterile needle and syringe. An appropriately graduated syringe must be used to allow accurate administration of the required dose volume. This is particularly important when injecting small volumes, for example when treating piglets. The cap may be safely punctured up to 25 times. The 50 ml vial should be used for treating small piglets. When treating groups of animals, use a draw-off needle. Swab the septum before removing each dose. Use a dry sterile needle and syringe. An appropriately graduated syringe must be used to allow accurate administration of the required dose volume. This is particularly important when injecting small volumes, for example when treating piglets. The cap may be safely punctured up to 25 times. The 50&nbsp;ml vial should be used for treating small piglets. When treating groups of animals, use a draw-off needle. -->


=== Caution/warnings === === Caution/warnings ===
These are some factors to be aware of before treating. These are some factors to be aware of before treating:
* This product should not be used in animals known to be hypersensitive to β-lactam antibiotics. * This product should not be used in animals known to be hypersensitive to β-lactam antibiotics.
* Should not be administered to animals with a body weight less than 1.25&nbsp;kg. * It should not be administered to animals with a body weight less than 1.25&nbsp;kg.
* Use of the product may result in localised tissue reaction. Tissue lesions are repaired by 15 days after the last administration of the product. * Use of the product may result in localised tissue reaction. Tissue lesions are repaired by 15 days after the last administration of the product.
* Hypersensitivity reactions to cephalosporins occur rarely. * Hypersensitivity reactions to cephalosporins occur rarely.
* The product does not contain an antimicrobial preservative. * The product does not contain an antimicrobial preservative.
* To prevent the claimed infections in piglets, attention should be paid to hygiene and ventilation, and overcrowding should be avoided. When the first piglets are affected, careful examination of all animals in the same pen is recommended to enable an early treatment of any other infected piglets. * To prevent the claimed infections in piglets, attention should be paid to hygiene and ventilation, and overcrowding should be avoided. When the first piglets are affected, careful examination of all animals in the same pen is recommended to enable an early treatment of any other infected piglets.


== Clinical usage == == Clinical usage ==

=== Human use === === Human use ===
Cefquinome is not approved for human use. Cefquinome is not approved for human use.


=== Veterinary medicine === === Veterinary medicine ===
Conditions of use are limited to therapeutic, parenteral, and individual animal use. Individual parenteral therapy of bovine respiratory disease data on cefquinome-related residues demonstrate that only very small amounts are present in the intestinal tract of treated cattle with gastrointestinal activation. Conditions of use are limited to therapeutic, parenteral, and individual animal use. Individual parenteral therapy of bovine respiratory disease data on cefquinome-related residues demonstrate only very small amounts are present in the intestinal tract of treated cattle with gastrointestinal activation. However, treatment should be short, meaning a single injection daily for about a week. Treatment should only be given by prescription. Cefquinome should not be used in feed or water.


⚫ Since 1994, in Europe, it was allowed to treat cattle by prescription only. In 1999, swine were included. By 2005, horses were allowed as well. In the United States, approval is pending for treatment of bovine respiratory disease. Even so, this is only available by prescription.
However, treatment should be short, meaning a single injection daily for about a week. Treatment should only be given by prescription. Cefquinome should not be used in feed or water.


⚫ Cefquinome is also used for other illnesses, such as “shipping fever”, a ]-like illness commonly found in cattle.<ref name="Farmers, doctors">Associated Press, "Farmers, doctors battle over new drug for dairy cows," April 5, 2007, State and Regional</ref>
⚫ Since 1994, in Europe, it was allowed to treat cattle by prescription only. In 1999, swine were included. By 2005, horses were allowed as well.


⚫ == Concerns ==
In the United States, approval is pending for treatment of bovine respiratory disease. Even so, this is only available by prescription.


⚫ Cefquinome are also used for other illnesses, such as “shipping fever,” a ]-like illness commonly found in cattle.<ref name="Farmers, doctors">Associated Press, "Farmers, doctors battle over new drug for dairy cows," April 5, 2007, State and Regional</ref>

⚫ == Concerns ==
=== Resistance and food-borne transmission === === Resistance and food-borne transmission ===
There are concerns that the use of the drug in animals will lead to increases in ]. Humans can be exposed to bacteria through food-borne transmission, raising chances of becoming exposed to resistant bacterial species, such as ] or ]. The potential for the development of antibiotic resistance increases as usage increases, by selecting bacteria which have acquired ]s. Of concern, the use of the drug in animals may lead to increases in ]. Humans can be exposed to bacteria through food-borne transmission, raising chances of becoming exposed to resistant bacterial species, such as '']'' or ''E. coli''. The potential for the development of antibiotic resistance increases as usage increases, by selecting bacteria which have acquired ]s.


=== Salmonella === === ''Salmonella'' ===
The use of CEQ may cause resistance in Salmonella present in the intestinal tract of the target animal. Resistant Salmonella may also contaminate the carcass at slaughter and transfer to humans when used as food. When humans are infected and treated with a 4GC, effectiveness may be compromised. The use may cause resistance in ''Salmonella'' present in the intestinal tract of the target animal. Resistant ''Salmonella'' may also contaminate the carcass at slaughter and transfer to humans when used as food. When humans are infected and treated with a fourth-generation cephalosporin, effectiveness may be compromised.


Although 4GC resistance is very rare, they are active against bacteria carrying the AmpC-type β-lactamase resistance mechanism. Since the late 1990s, the US and EU have surveyed and gathered data for 4GCs for both human and veterinary use. Data indicate that there are no changes in resistance patterns of relevant food-borne pathogens. Although fourth-generation cephalosporin resistance is very rare, they are active against bacteria carrying the AmpC-type β-lactamase resistance mechanism. Since the late 1990s, the US and EU have surveyed and gathered data for fourth-generation cephalosporins for both human and veterinary use. Data indicate no changes occur in resistance patterns of relevant food-borne pathogens.


== FDA guidelines == == FDA guidelines ==
*Administered products will be used in individual animals for short duration and by prescription only. * Administered products will be used in individual animals for short duration and by prescription only.
*The extent of use is ranked low. * The extent of use is ranked low.
*Avoid human drug resistance to fourth-generation cephalosporins by authorizing extra-label prohibition. * Avoid human drug resistance to fourth-generation cephalosporins by authorizing extra-label prohibition.
== Synthesis ==

Broad-spectrum fourth generation injectable {{chem name|aminothiazolyl}} cephalosporin.
== Footnotes ==
]).</ref><ref>{{cite journal | vauthors = Brown RF, Kinnick MD, Morin JM, Vasileff RT, Counter FT, Davidson EO, Ensminger PW, Eudaly JA, Kasher JS, Katner AS | display-authors = 6 | title = Synthesis and biological evaluation of a series of parenteral 3'-quaternary ammonium cephalosporins | journal = Journal of Medicinal Chemistry | volume = 33 | issue = 8 | pages = 2114–2121 | date = August 1990 | pmid = 2115587 | doi = 10.1021/jm00170a011 }}</ref>]]
<references/>
] ('''1''') is a potent cephalosporin antibiotic in its own right. Further modification of this drug by inclusion of a ] gives a compound suitable for ] by increasing ]. The acid in ] is first protected as its silyl ester ('''2''') by derivatization with ''N''-methyl-''N''-(trimethylsilyl)trifluoroacetamide (]). Treatment of this intermediate with ] gives the allylic iodide ('''3'''). Displacement of halogen with ]<ref>{{cite journal |doi=10.1055/s-1979-28630 |title=A Convenient Synthesis of 5,6,7,8-tetrahydroquinoline |journal=Synthesis |volume=1979 |issue=3 |pages=221–223 |year=1979 | vauthors = Kusumi T, Yoneda K, Kakisawa H |s2cid=94461736 }}</ref> (]) gives the corresponding quaternary salt. Hydrolysis of the silyl ester followed by adjustments of the ] leads to the ] cefquinome ('''4''').


== See also == == See also ==
*] * '']''
*] * ]
*] * ]
*] * ]
*] * ]
*]
*]


== References == == References ==
{{Reflist}}
*“Farmers, doctors battle over new drug for dairy cows.” ''Associated Press''. 5 Apr 2007.

*Belongia, Edward. “Beware wider use of antibiotics in animals.” ''Star Tribune''. 9 Apr 2007.
== Further reading ==
*“Efficacy of Cefquinome.” ''Journal of Dairy Science'', Vol. 80, No. 2, 1997.
{{refbegin}}
*"Cephaguard Injection Data Sheet." ''Intervet''. <http://www.intervet.co.uk/Products_Public/Cephaguard_Injection/090_Product_Datasheet.asp> July 2006.
* {{cite journal | vauthors = Shpigel NY, Levin D, Winkler M, Saran A, Ziv G, Böttner A | title = Efficacy of cefquinome for treatment of cows with mastitis experimentally induced using Escherichia coli | journal = Journal of Dairy Science | volume = 80 | issue = 2 | pages = 318–323 | date = February 1997 | pmid = 9058274 | doi = 10.3168/jds.S0022-0302(97)75941-1 | doi-access = free }}
*Johnson, Carl K. "Introduction to Cefquinome (CEQ) and Overview of Microbial Safety Assessment." <http://www.fda.gov/cvm/VMAC/VMAV0906Johnson.htm> 20 Sept 2006.
* {{cite web | title = Cephaguard Injection Data Sheet | work = Intervet | url = http://www.intervet.co.uk/Products_Public/Cephaguard_Injection/090_Product_Datasheet.asp | date = July 2006 | archive-url = https://web.archive.org/web/20050115193430/http://www.intervet.co.uk/Products_Public/Cephaguard_Injection/090_Product_Datasheet.asp | archive-date = 2005-01-15 }}
*Weiss, Rick. "FDA rules override warnings about drug." ''The Washington Post''. 4 Mar 2007.
* {{cite web | vauthors = Johnson CK | title = Introduction to Cefquinome (CEQ) and Overview of Microbial Safety Assessment. | publisher = U.S. Food and Drug Administration | url = https://www.fda.gov/cvm/VMAC/VMAV0906Johnson.htm | archive-url = https://web.archive.org/web/20080514145531/https://www.fda.gov/cvm/VMAC/VMAV0906Johnson.htm | archive-date = 14 May 2008 |date = 20 September 2006 }}
{{refend}}


== External links == == External links ==
* * {{cite web | url = http://www.intervet.co.uk/Products_Public/Cephaguard_Injection/090_Product_Datasheet.asp | title = Intervet Product Datasheet | work = Intervet | archive-url = https://web.archive.org/web/20050115193430/http://www.intervet.co.uk/Products_Public/Cephaguard_Injection/090_Product_Datasheet.asp | archive-date = 2005-01-15 }}
*
*


{{Cell wall disruptive antibiotics}} {{Cell wall disruptive antibiotics}}

] ]
] ]
] ]
] ]

]