拙笨Cephalothin
Eric Scholar University of Nebraska Medical Center,Omaha,USA
ã2007Elvier Inc.All rights rerved.
Introduction
Cephalothin is a misynthetic,first-generation cephalosporin that is derived from cephalosporin C,a natural antibiotic.It was one of the first cephalosporins introduced for clinical u.As a first-generation cephalosporin it has excellent activity against a variety of gram-positive infections,while its activity against gram-negative infections is inferior to later generation cephalosporins.While cephalothin is rarely a drug of choice for the treatment of infections it is ud primarily for prophylaxis in various surgical procedures such as prosthetic heart valve inrtion and gastrointestinal surgery.Becau cephalothin is not absorbed following oral administration it must be ud parenterally.Allergic reactions are among the most common adver effects with this agent.
Nomenclature
Name of the Clinical Form Cephalothin sodium
Related Names Source:EMTREE Cephalothin;5-Tia-1-azabicyclo[4.2.0.]oct-2-ene-
2-carboxylic acid,3-((acetyloxy)methyl)-8-oxo-7-((2-thienyllacetyl)amino)-,(6R-trans)-;Keflin(trade); cefalothin;cefalothin sodium;cefalotine;cefalotin sodium;cefalotin sodium salt;cefalozin;cefolotin; cephalosin;cephalosporin871;cephalothine; cephalothin sodium;cephalotin;cephalotine; cephalotin sodium;cephation;ceporacin; cepovenin;keflin;microtin;ffin;sodium cephalothin;sodium cephalotin;7
(2thienylacetamido)cephalosporanic
acid;cefalotin;
空间组织5-Tia-1-azabicyclo[4.2.0.]oct-2-ene-2-carboxylic acid,3-((acetyloxy)methyl)-8-oxo-7-
((2-thienyllacetyl)amino)-,(6R-trans)-
Chemical Names7-(thiophene-2-acetamido)-cephalosporanic acid;
7-(2-thienylacetamido)cephalosporanic acid
CAS Number153-61-7
1
Basic Chemistry
Chemical Structure
Structure
Chemical Formula C16H16N2O6S2
Properties
Physical Properties Cephalothin is a white to off-white,crystalline powder
that is practically odorless and is moderately
hygroscopic.Its m.p.is204–205 C.It has UV max
of236and260nm.
Molecular Weight396.442
Solubility Cephalothin is freely soluble in water,normal saline,or
dextro solution.It is slightly soluble in ethanol and
insoluble in most organic solvents.
Ionization Constant
Value Salt Conditions Reference Comments pKa 2.2Gennaro(2002)
Human Pharmacokinetics
Becau cephalothin is not well absorbed following oral administration it is given paren-terally,usually i.v.,becau of pain at the site injection.Cephalothin penetrates very poorly into the cerebrospinal fluid,even in the prence of meningitis.It is rapidly deacetylated,mainly in the liver,
producing the metabolite,desacetylcephalosporin.It is excreted primarily in urine,mainly by tubular cretion.About65%of an administered do of cephalothin is excreted unchanged with the rest as the metabolite.Cephalothin has a relatively short half-life Petri(2001),Drugdex(2003),Scholar and Pratt(2000).
Pharmacokinetic Properties
Value Units Prep.and Route of
Admin.Reference Comments
Absorption Cephalothin is poorly absorbed following oral administration,but well-absorbed injection.
Lane et al(1977)
Distribution
Volume of Distribution 0.21–0.26l/kg i.v.Kirby and Regamey
(1973)
Cephalothin 2
Plasma Protein Binding 70%i.v.Marshall and
Blair(1999)
Metabolism Cephalothin is rapidly deacetylated in the liver,yielding desacetylcephalosporin, which also has antibacterial activity.
Plasma Half-Life0.67hrs i.v.Marshall and
Blair(1999)
Bio Half-Life
Clearance274–300ml/min/kg i.v.Kirby and
Regamey(1973)
Routes of Elimination Cephalothin is excreted in large quantities in urine,primarily by tubular cretion. About65%of an administered do is excreted unchanged,with the rest as metabolite.
Targets-Pharmacodynamics
Cephalothin is a first-generation cephalosporin.Like other cephalosporins it is a bacteri-cidal antibiotic that inhibits cell wall synthesis of actively dividing cells by binding to one or more penicillin binding proteins.The result is formation of a defective cell wall that is osmotically unstable.Cephalosporins,like penicillins,may increa the breakdown of the cell wall of bacteria by decreasing the availability of an inhibitor of murein hydrola (autolysin),an enzyme involved in cell division Drugdex(2003),Scholar and Pratt(2000). Target Name(s):
Penicillin binding proteins
Therapeutics
Cephalothin is a uful alternative to penicillin G for the treatment of streptococcal and pneumococcal infections.Although it is less effective,its ud primarily in penicillin-allergic patients.It is also employed to treat certain staphylococcal infections in penicil-lin-allergic patients.Since,among the cephalosporins,cephalothin is the most impervious to attack by staphylococcal B-lactama,it is very effective in vere staphylococcal infections,such as endocarditis.It is also ud to prevent infections prior to surgery. Although reprentative dos are given below,the current literature indica
tes that dos range from500mg–2g every4–6hrs Petri(2001),Drugdex(2003),Kucers et al(1997). Indications
Value Units Prep.and Route
of Admin.
Reference Comments
Surgical Prophylaxis(cardiac,gastrointestinal,gynecological,orthopedic,thoracic,and vascular surgeries)
Dosage1–2g i.v.just prior to
surgery,then1–2
g during surgery
and
postoperatively
every6hrs for
24hrs Raab et al(1982),
Condon et al
(1983),Bivens
et al(1975),
Burnett et al
(1980),Cameron
et al(1981),May
et al(1980)
Cephalothin is often
蒜苗的营养价值combined with an
aminoglycoside
antibiotic or
metronidazole.
引言Cephalothin3
Bone and Joint Infections (caud by susceptible Staphylococci)
Dosage 500mg i.v.,every 6hrs Product Information
Keflin (1996)Two grams every 4hours are ud
for life-threatening
infections.
Gastrointestinal Infections (caud by susceptible Salmonella and Shigella)
Dosage 500mg i.v.,every 6hrs Product Information Keflin (1996)Two gram every
4hours are ud
for life-threatening
infections.
Respiratory Tract infections (rious infections caud by susceptible Streptococci,Staphylococci,Klebsiella and Haemophilus influenzae)
Dosage 500mg i.v.,every 6hrs Product Information Keflin (1996)Two grams every
4hours are ud
for life-threatening
infections.
Urinary Tract Infections
Dosage 500mg i.v.,every 6hrs Product Information
Keflin (1996)
Contraindications
Cephalothin is contraindicated for tho known to be hypernsitive to cephalosporins.Adver Effects
Hypernsitivity is the most frequently encountered reaction to cephalothin,including rashes and anaphylaxis.There also may be pain,induration,and tenderness associated u and thrombophlebitis associated with i.v.administration.Other possible adver effects associated with the u of this agent include agranulocytosis,hemolytic anemia,pancytopenia,and thrombocytopenia.The cephalosporins are potentially neph-rotoxic but not nearly as much as the aminoglycosides and polymyxins Petri (2001),Kucers et al (1997),Drugdex (2003).
Agent-Agent Interactions
Agent Name
Mode of Interaction Aminoglycosides
There is an incread risk of nephrotoxicity with concurrent u of cephalothin and aminoglycoside antibiotics.Live typhoid vaccine Antibiotics that are effective against salmonella typhi organism may
interfere with the immunological respon to the live typhoid
65000日元vaccine Product Information Vivotif (1997).
Probenecid
By inhibiting renal tubular cretion,probenecid delays the excretion
of cephalothin.Pre-Clinical Rearch
Cephalothin is effective against gram-positive organisms,more so than the cond-and third-generation cephalosporins.Its activity is good against most staphylococci,including penicillina-producing strains.Cephalothin is also effective against some strains of Escherichia coli,Klebsiella and Proteus mirabilis .In vitro cephalothin is active against Cephalothin
4
Hemophilus influenzae,but less so than cond-generation cephalosporins.It is also active against Neisria gonorrhea,ingitides,Salmonella and Shigella.It lacks activity against Pudomonas as well as indole-producing Proteus and Enterobacter Drugdex (2003),Kucers et al(1997).
Pharmacokinetics
Potency
Value Units Organ/
Tissue Prep.
and
Route
of
Admin.
Cell
Line/
Type
Effects Exp.
End
Point
Reference Comments
Mou
LD50>2000mg/O’Neil et al
(2001)
LD505679mg/kg i.p.O’Neil et al
(2001)
Rat
LD50>1000mg/O’Neil et al
(2001)
LD507716mg/kg i.p.O’Neil et al
(2001)
Other Information–Web Sites
Micromedex general drug information:
library1.unmc.edu:2048/login?url=/mdxcgi/mdxhtml.
exe?&1&SCRNAME=hcssrch1&CTL=d:/mdx/mdxcgi/megat.sys General drug /druginfo
Journal Citations
Marshall,W.F.,Blair,J.E.,1999.The Cephalosporins.Mayo Clin.Proc.,74,187–195.
Lane,A.Z.,Chudzik,G.M.,Siskin,S.B.,1977.Comparative pharmacokinetic studies of cephapirin and
cephalothin following intravenous and intramuscular administration.Curr.Ther.Res.Clin.Exp.,21,
117–127.
Kirby,W.M,Regamey,C.,1973.Pharmacokinetics of cefazolin compared with four other cephalosporins.
J.Infect.Dis.,128(Suppl),S341–S346.
Cameron,J.L.,Imbembo,A.,Kieffer,R.F.,Spray,S.,Baker,R.R.,1981.Prospective clinical trial of
antibiotics for pulmonary rections.Surg.Gynecol.Obstet.,152,156–158.
Bivens,M.D.,Neufeld,J.,McCarthy,W.D.,1975.The prophylactic u of Keflex and Keflin in vaginal hysterectomy.Am.J.Obstet.Gynecol.,122,169–175.
Burnett,J.W.,Gustilo,R.B.,Williams,D.N.,Kind,A.C.,1980.Prophylactic antibiotics in hip fractures:a
double-blind prospective study.J.Bone Joint Surg.,62A,457–462.
Condon,R.,Bartlett,J.G.,Greenlee,H.,Schulte,W.J.,Ochi,S.,Abbe,R.,Caruana,J.A.,Gordon,H.E.,
天秤摩羯
Horsley,J.S.,Irvin,G.III,Johnson,W.,Jordan,P.Jr.,Keitzer,W.F.,Lempke,R.,Read,R.C.,Schumer,
W.,Schwartz,M.,Storm,F.K.,Vetto,R.M.,1983.Efficacy of oral and systemic antibiotic prophylaxis in
colorectal operations.Arch.Surg.,118,496–502.
宏村写生
May,A.R.,Darling,R.C.,Brewster,D.C.,Darling,C.S.,1980.A comparison of the u of cephalothin and
千牛刀oxacillin in vascular surgery.Arch.Surg.,115,56–59.
Cephalothin5
Raab,T.A.,Balderman,S.,Bhayana,J.,Bingham,K.,Mylotte,J.,Beam,T.R.Jr.,1982.A comparison of the safety,efficacy,and distribution of ceforanide and cephalothin in coronary artery bypass graft surgery.Ann.Thorac.Surg.,33(4),340–344.
Book Citations
Gennaro,A.R.,2002.Gennaro,A.R.(Ed.),Remington:The Science and Practice of Pharmacy ,Edition 20.,Lippincott Williams and Wilkins,Philadelphia,PA.
Kucers,A.,Crowe,S.M,Grayson,M.L.,Hoy,J.F.,1997.Cephalothin and Cephaloridine.The U of Antibi
otics.A Clinical Review of Antibacterial,Antifungal and Antiviral Drugs ,Edition 5,pp.251–262,Butterworth Heinemann,Oxford,England.
Scholar,E.M.,Pratt,W.,2000.The Inhibitors of Cell Wall Synthesis,II Pharmacology and Adver Effects of the Penicillins,Cephalosporins,Carbapenems,Monobactams,Vancomycin and Bacitracin.The Antimicrobial Drugs ,Edition 2,pp.81–125,Oxford Univ.Press,NY,NY.
Petri,W.A.,2001.Penicillins,Cephalosporins,and Other B-Lactam Antibiotics.1189-1218,Hardman,J.G.,Limbird,L.E.(Ed.),Goodman and Gilman’s The Pharmacological Basis of Therapeutics ,Edition 10.,McGraw Hill,NY,NY.
O’Neil,M.J.,Smith,A.,Heckelman,P.E.,2001.O’Neil,M.J.,Smith,A.,Heckelman,P.E.(Ed.),Merck Index ,Edition 13.,Merck and Co.,Inc.,Whitehou Station,NJ.
Drugdex,2003.Micromedex (Online Version).Micromedex Inc.,Englewood,CO.
Product Information Keflin,1996.Product information:Keflin W ,cephalothin .Eli Lilly,Indianapolis,IN.Product Information Vivotif,1997.Product information Vivotif Berna Vaccine,typhoid vaccine live oral ty21a .Berna Products Corp.,Coral Cables,FL.Cephalothin
6
