CEPHALORIDINE

First approved in 1968

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H17N3O4S2
Molecular Weight	415.486
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12SCC(C[N+]3=CC=CC=C3)=C(N1C(=O)[C@H]2NC(=O)CC4=CC=CS4)C([O-])=O

InChI

InChIKey=CZTQZXZIADLWOZ-CRAIPNDOSA-N

InChI=1S/C19H17N3O4S2/c23-14(9-13-5-4-8-27-13)20-15-17(24)22-16(19(25)26)12(11-28-18(15)22)10-21-6-2-1-3-7-21/h1-8,15,18H,9-11H2,(H-,20,23,25,26)/t15-,18-/m1/s1

HIDE SMILES / InChI

Description
Sources: http://www.druginfosys.com/Drug.aspx?drugCode=149&drugName=Cephaloridine&type=6
Curator's Comment: Description was created based on several sources. including http://www.drugbank.ca/drugs/DB09008 and http://onlinelibrary.wiley.com/doi/10.1002/cpt196896819/abstract

Cephaloridine (or cefaloridine) is a first generation semisynthetic derivative of cephalosporin C. It is unique among cephalosporins in that it exists as a zwitterion. It is of semi synthetic origin and belongs to cephem carboxylate. It belongs to Peptidoglycan synthesis inhibitor pharmacological group on the basis of mechanism of action. Since the discovery of cephalosporins P, N and C in 1948 there have been many studies describing the antibiotic action of cephalosporins and the possibility to synthesize derivatives. Hydrolysis of cephalosporin C, isolation of 7-aminocephalosporanic acid and the addition of side chains opened the possibility to produce various semi-synthetic cephalosporins. In 1962, cephalothin and cephaloridine were introduced. Cephaloridine is very active against gram positive cocci and used in a large variety of bacterial infections, such as respiratory tract, skin and urinary tract infections. Cephaloridine is primarily indicated in conditions like Bacterial infections, Bronchitis, Gonorrhoea, and can also be given in adjunctive therapy as an alternative drug of choice in Corneal ulcers, Intraocular infections. Cephaloridine was temporarily popular because it was better tolerated intramuscularly and attained in higher and more sustained levels in blood than cephalothin. Because it is also poorly absorbed after oral administration the use of this drug for humans declined rapidly, especially since the second generation of cephalosporins was introduced in the 1970s. Today it is more commonly used in veterinary practice to treat mild to severe bacterial infections caused by penicillin resistant and penicillin sensitive Staphylococcus aureus, Escherichia coli, Streptococcus pyogenes, Streptococcus pneumoniae, Bacillus sutbtilis, Klebsiella, Clostridium diptheriae, Salmonella and Shigella. Before the 1970s, cephaloridine was used to treat patients with urinary tract infections. Besides the drug has been used successfully in the treatment of various lower respiratory tract infections. Cephaloridine was very effective to cure pneumococcal pneumonia. It has a high clinical and bacteriological rate of success in staphylococcal and streptococcal infections.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
D-alanyl-D-alanine carboxypeptidase DacC 3 Target ID: P39844 Gene ID: 939990.0 Gene Symbol: dacC Target Organism: Bacillus subtilis (strain 168) Sources: http://www.ncbi.nlm.nih.gov/pubmed/11160090	Inhibitor 8297
Rabbit proximal tubules 1 Target ID: Rabbit proximal tubules Sources: http://www.ncbi.nlm.nih.gov/pubmed/2068729	Inhibitor 8297	1.1 mM [EC50]
Solute carrier family 22 member 5 3 Target ID: CHEMBL2073693 Sources: http://www.ncbi.nlm.nih.gov/pubmed/10636865	Inhibitor 8297	0.23 mM [IC50]
Solute carrier family 22 member 6 19 Target ID: CHEMBL1641347 Sources: http://www.ncbi.nlm.nih.gov/pubmed/10929807	Inhibitor 8297	1250.0 µM [IC50]
Solute carrier family 22 member 7 5 Target ID: CHEMBL1955711 Sources: http://www.ncbi.nlm.nih.gov/pubmed/12650826	Inhibitor 8297	4.48 mM [IC50]
Escherichia coli growth 23 Target ID: Escherichia coli growth Sources: http://www.ncbi.nlm.nih.gov/pubmed/18765691	Inhibitor 8297
Peptidoglycan biosynthesis 20 Target ID: map00550 Sources: http://www.kegg.jp/entry/D01075	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Respiratory tract infections 85 Sources: http://www.medclik.com/General/pages/Drugmanual/BrandSearch9/CEPORAN.asp	Curative	Approved 8429	Ceporan Approved Use Respiratory tract infections, Septicemia, Skin & Soft tissue infections, Urinary tract & genital tract infections, Surgical prophylaxis
Urinary tract infections 205 Sources: http://drugbook.in/ceporan-500mg.html	Curative	Approved 8429	Ceporan Approved Use Respiratory tract infections, Septicemia, Skin & Soft tissue infections, Urinary tract & genital tract infections, Surgical prophylaxis
Sepsis 71 Sources: http://www.medclik.com/General/pages/Drugmanual/BrandSearch9/CEPORAN.asp	Curative	Approved 8429	Ceporan Approved Use Respiratory tract infections, Septicemia, Skin & Soft tissue infections, Urinary tract & genital tract infections, Surgical prophylaxis

C_max

Value	Dose	Co-administered	Analyte	Population
38 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/278145/	1 g single, intramuscular dose: 1 g route of administration: Intramuscular experiment type: SINGLE co-administered:		CEPHALORIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
40 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/278145/	1 g single, intramuscular dose: 1 g route of administration: Intramuscular experiment type: SINGLE co-administered:		CEPHALORIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/278145/	1 g single, intramuscular dose: 1 g route of administration: Intramuscular experiment type: SINGLE co-administered:		CEPHALORIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
69% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/278145/	1 g single, intramuscular dose: 1 g route of administration: Intramuscular experiment type: SINGLE co-administered:		CEPHALORIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT2 145 PEPT1 20 OAT1 599 OAT3 642 OAT4 146 OCTN2 66	OCTN2 50 OAT1 326 OAT3 339

Drug as perpetrator

Target	Modality	Activity
OCTN2 71	inhibitor 3277 Sources: http://transportal.compbio.ucsf.edu/compounds/cephaloridine/, https://www.jbc.org/article/S0021-9258(18)31098-6/fulltext	yes [IC50 230 uM]
OAT2 147	inhibitor 3277 Sources: https://pubs.rsc.org/EN/content/chapterhtml/2015/bk9781849738286-00001?isbn=978-1-84973-828-6&sercode=bk, http://transportal.compbio.ucsf.edu/compounds/cephaloridine/, https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [IC50 4480 uM]
OAT3 644	inhibitor 3277 Sources: http://transportal.compbio.ucsf.edu/compounds/cephaloridine/, https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [Ki 2460 uM]
OAT4 146	inhibitor 3277 Sources: http://transportal.compbio.ucsf.edu/compounds/cephaloridine/, https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [Ki 3630 uM]
OAT1 603	inhibitor 3277 Sources: http://transportal.compbio.ucsf.edu/compounds/cephaloridine/, https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [Ki 740 uM]
PEPT1 22	inhibitor 3277 Sources: https://pubs.rsc.org/EN/content/chapterhtml/2015/bk9781849738286-00001?isbn=978-1-84973-828-6&sercode=bk	yes

Drug as victim

Target	Modality	Activity
OAT1 326	substrate 3367 Sources: https://www.taylorfrancis.com/books/principles-biochemical-toxicology-john-timbrell/10.3109/9781420007084, https://go.drugbank.com/drugs/DB09008, https://pubmed.ncbi.nlm.nih.gov/19953504/ Page: 332-335	yes
OAT3 339	substrate 3367 Sources: https://go.drugbank.com/drugs/DB09008, https://pubmed.ncbi.nlm.nih.gov/19953504/	yes
OCTN2 50	substrate 3367 Sources: https://www.annualreviews.org/doi/abs/10.1146/annurev.pharmtox.44.101802.121444	yes

Sourcing

Vendor/Aggregator	ID	URL
ABI Chem	AC1L1L3T
Ambinter	Amb23401101	http://www.ambinter.com/reference/23401101
AmicBase - Antimicrobial Activities	5138
Aurora Fine Chemicals LLC	A17.918.340	http://online.aurorafinechemicals.com/info?ID=A17.918.340
BOC Sciences	50-59-9
BePharm Ltd.	B120380
BenchChem	B523063	https://www.benchchem.com/product/b523063
Chemieliva Pharmaceutical Co., Ltd	PBCM0603728
Chemspace	CSSB00020627542	https://chem-space.com/CSSB00020627542
Compound Cloud	5773
Compound Cloud	5774
Hairui	HR143713	http://www.hairuichem.com/en/product/50-59-9.html
MuseChem	I005918
Norris Pharm	NSZB-A011214
NovoSeek	5773
Oxchem Corporation	AX8120380
PI Chemicals	PI-39101
Smolecule	S523063	http://www.smolecule.com/products/s523063
Smolecule	S772632	https://www.smolecule.com/products/s772632
THE BioTek	bt-263294	https://www.thebiotek.com/product/inhibitors/bt-263294
Yick-Vic Chemicals & Pharmaceuticals (HK) Ltd.	PH-0142
ZINC	ZINC000001532351	http://zinc15.docking.org/substances/ZINC000001532351
ZINC	ZINC000003202698	http://zinc15.docking.org/substances/ZINC000003202698
ZINC	ZINC000003202700	http://zinc15.docking.org/substances/ZINC000003202700
ZINC	ZINC000003202703	http://zinc15.docking.org/substances/ZINC000003202703
eMolecules	106943421
eMolecules	46015071
eMolecules	50221528
eNovation Chemicals	D676125	https://www.enovationchem.com/ProductDetails.asp?ProductID=D676125
mcule	MCULE-8657732741

PubMed

Title	Date	PubMed
Nephrotoxicity associated with the use of cephaloridine.	1967 May 22	6071504
Penicillin-induced haemolytic anaemia.	1968 Jul 6	5661907
Renal damage associated with prolonged administration of ampicillin, cephaloridine, and cephalothin.	1969	5396519
[Nephrotoxicity of cephaloridine. 3 cases of acute renal failure with anuria].	1969 Oct 18	4982004
The nephrotoxicity of cephaloridine.	1970 Oct	5488206
Reversible encephalopathy and acute renal failure after cephaloridine.	1970 Oct 31	5475848
Parkinsonism syndrome due to cephaloridine.	1971 May 17	5108409
Nephrotoxicity and acute renal failure associated with cephalothin and cephaloridine.	1971 Nov	5289757
Nephrotoxicity of cephaloridine.	1971 Oct 9	5097409
Relative nephrotoxicity of cephalosporin antibiotics in an animal model.	1972 Sep 9	5074752
[Acute renal failure following combined cephaloridine-gentamycin therapy (author's transl)].	1973 Dec 21	4589000
Convulsion following intrathecal cephaloridine.	1975	1242383
Cephaloridine, cephalothin and the kidney.	1975	1201976
Relationship between the transport and toxicity of cephalosporins in the kidney.	1975 Aug	1159324
Acute renal failure associated with cephalosporin therapy.	1975 Jun	1130272
Renal and hepatic necrosis after metabolic activation of 2-substituted furans and thiophenes, including furosemide and cephaloridine.	1977 Nov	595008
Renal tubular necrosis following cephalothin.	1979	471144
Cephaloridine encephalopathy.	1981 Aug 8	6789989
IgE antibodies for penicillins and cephalosporins in rats. III. Antigenic specificity of rat anti-cephalosporin-OvA IgE sera.	1981 Jan	6166604
Nephrotoxicity of cefotiam (CGP 14221/E) in rats and rabbits.	1981 Sep	6271094
Renal tolerance of ceftazidime in animals.	1981 Sep	19802993
In vitro and in vivo susceptibility of atypical mycobacteria to various drugs.	1981 Sep-Oct	7339820
[Studies on the nephrotoxicity of cephaloridine in the mouse (author's transl)].	1982	7201831
Lipid peroxidation: a possible mechanism of cephaloridine-induced nephrotoxicity.	1983 Jan	6845359
Ceftazidime nephrotoxicity in rats.	1984 Apr	6375559
Vasopressin-resistant polyuria induced by cephaloridine administration in rats.	1986	3829983
Biochemical mechanisms of cephaloridine nephrotoxicity.	1988	3285106
Neurotoxicity of beta-lactam antibiotics. Experimental kinetic and neurophysiological studies.	1988	3241957
The use of renal cortical slices from the Fischer 344 rat as an in vitro model to evaluate nephrotoxicity.	1988 Jul	2905310
Protective effect of piperacillin against nephrotoxicity of cephaloridine and gentamicin in animals.	1988 Jun	3415211
[Nephrotoxicity of cefodizime sodium in rats--single and 14-day repeated intravenous administration].	1988 Jun	3172294
Relieving effect of saline on cephaloridine nephrotoxicity in rats.	1989 Mar	2752494
[Acute renal failure caused by ceporin, kanamycin and gentamicin].	1989 Mar-Apr	2728142
Safety evaluation of meropenem in animals: studies on the kidney.	1989 Sep	2681127
Drugs as allergens: an immunoassay for detecting IgE antibodies to cephalosporins.	1990	2083978
Methimazole protection of rats against chemically induced kidney damage in vivo.	1992 Jan	1731048
Cephaloridine nephrotoxicity is potentiated by selenium deficiency but not copper deficiency in rats.	1992 Jun	1588439
[Study on gamma-GTP activity in urine and renal tissue of drug-induced nephrotoxicity in rats].	1993 Jul	8102655
Effects of KW-3902, a novel adenosine A1-receptor antagonist, on cephaloridine-induced acute renal failure in rats.	1994 Jan	8164396
Magnesium lithospermate B ameliorates cephaloridine-induced renal injury.	1997 Dec	9455678
Effect of ginsenoside-Rd in cephaloridine-induced renal disorder.	1999 Feb	9933756
Enhancement of protein kinase C activity and chemiluminescence intensity in mitochondria isolated from the kidney cortex of rats treated with cephaloridine.	2002 Aug 1	12147306
beta-Lactam allergenic determinants: fine structural recognition of a cross-reacting determinant on benzylpenicillin and cephalothin.	2002 Nov	12569987
Protective effect of serum thymic factor, FTS, on cephaloridine-induced nephrotoxicity in rats.	2005 Nov	16272694
Serum thymic factor, FTS, attenuates cisplatin nephrotoxicity by suppressing cisplatin-induced ERK activation.	2005 Nov 1	16154539
Human organic anion transporter hOAT3 is a potent transporter of cephalosporin antibiotics, in comparison with hOAT1.	2005 Oct 1	16098483
Transcriptomic analysis of nephrotoxicity induced by cephaloridine, a representative cephalosporin antibiotic.	2008 Jun	18500788
In vitro gene expression analysis of nephrotoxic drugs in rat primary renal cortical tubular cells.	2008 Mar	18172885
Kidney injury molecule-1 expression in rat proximal tubule after treatment with segment-specific nephrotoxicants: a tool for early screening of potential kidney toxicity.	2010 Apr	20305092
In vitro and in vivo efficacy of β-lactams against replicating and slowly growing/nonreplicating Mycobacterium tuberculosis.	2013 Jun	23507276

Patents

Sample Use Guides

In Vivo Use Guide

1gm to1.5gm daily in two or three divided doses I.M. or I.V. In severe infections: 1.5 gm 8 hourly or 12 hourly. Children: 15 to 30 mg/kg/d.

Route of Administration: Intramuscular

In Vitro Use Guide

Against meningococci cephaloridine inactivated all strains at concentrations below 0.5 ug/ml

Name

Type

Language

CEPHALORIDINE

Official Name

English

CEFALORIDINE

Official Name

English

CEPHALORIDINE [MI]

Common Name

English

CEPHALORIDINE [USAN]

Common Name

English

CEPHALORIDINE [HSDB]

Common Name

English

7-(.ALPHA.-(2-THIENYL)ACETAMIDO)-3-(1-PYRIDYLMETHYL)-3-CEPHEM-4-CARBOXYLIC ACID BETAINE

Common Name

English

CEFALORIDINE [MART.]

Common Name

English

CEFALORIDINE [JAN]

Common Name

English

Cefaloridine [WHO-DD]

Common Name

English

cefaloridine [INN]

Common Name

English

40602

Code

English

PYRIDINIUM, 1-((2-CARBOXY-8-OXO-7-((2-THIENYLACETYL)AMINO)-5-THIA-1-AZABICYCLO(4.2.0)-OCT-2-EN-3-YL)METHYL)-, HYDROXIDE, INNER SALT, (6R-TRANS)-

Common Name

English

((6R,7R)-1-((2-CARBOXY-8-OXO-7-(2-(2-THIENYL)ACETAMIDO)-5-THIA-1-AZABICYCLO(4.2.0)OCT-2-EN-3-YL)METHYL)PYRIDINIUM HYDROXIDE, INNER SALT

Common Name

English

Classification Tree Code System Code

WHO-VATC

QJ01DB02