Ceftazidime
Sharon S.Castle VA Medical Center,Huntington,USA
ã2007Elvier Inc.All rights rerved.
Introduction
Ceftazidime is a parenteral,third-generation cephalosporin antibiotic that is administered by intravenous or intramuscular injection.It is effective against a wide variety of gram-negative organisms,including Pudomonas aeruginosa.Although ceftazidime is active in vitro against gram-positive organisms,clinical u of ceftazidime for gram positive infec-tions is rare.Ceftazidime is ud for the treatment of meningitis,lower respiratory infections,febrile neutropenic events,urinary tract infections,pelvic inflammatory dis-ea,and skin and skin structure infections.
Nomenclature
Name of the Clinical
Form
Ceftazidime sodium
Related Names Source:EMTREE Ceftazidime;7[2(2aminothiazol4yl)1(1carboxy
1methylethoxyimino)acetamido]3(1pyridiniomethyl)
2cephem2carboxylate;7[2(2aminothiazol4yl) glyoxylamido]3(pyrid1ylmethyl)2cephem2carboxylic acid betaine72[o(1carboxy1methylethyl)oxime]; ceftazadine;ceftazidime sodium;ceph2em2carboxylic acid betaine72[o(1carboxy1methylethyl)oxime],7[2(2 aminothiazol4yl)glyoxylamido]3(pyrid1ylmethyl);cmi90; foraz;fortam;fortaz;fortum;glazidim;gr20263;ly139381; modacin;sn401;solvetan;tazicef;tazidime;7[2(2 aminothiazol4yl)1(1carboxy1methylethoxyimino) acetamido]3(1pyridiniomethyl)2cephem2carboxylate;7 [2(2aminothiazol4yl)glyoxylamido]3(pyrid1ylmethyl)
2cephem2carboxylic acid betaine72[o(1carboxy1 methylethyl)oxime];ceph2em2carboxylic acid betaine7 2[o(1carboxy1methylethyl)oxime],7[2(2aminothiazol4yl) glyoxylamido]3(pyrid1ylmethyl);cmi90;gr20263;ly 139381;sn401
Chemical Names(Z)-(7R)-7-[2-(2-Aminothiazol-4-yl)-2-(1-carboxy-1-
methylethoxyimino)acetamido]-3-(1-pyridiniomethyl)-3-
cephem-4-carboxylate pentahydrate Sweetman(2003)
CAS Number72558-82-8
1
Basic Chemistry
Chemical Structure
Structure
Chemical Formula C22H22N6O7S2
牛奶木瓜汤
Properties
Physical Properties Ceftazidime is a white to cream-colored,crystalline powder
Sweetman(2003).
Molecular Weight546.583
Solubility Ceftazidime is slightly soluble in water,in dimethylformamide,
and in methyl alcohol.It is insoluble in alcohol,in acetone,in
chloroform,in dioxan,in ether,in ethyl acetate,and in toluene,
and is soluble in alkali and in dimethyl sulfoxide.The pH of a
0.5%aqueous solution is between3.0and4.0Sweetman
(2003).
Ionization Constant
Value Salt Conditions Reference Comments pKa 1.8Williams(2002)HA
pKa 2.7Williams(2002)HA
pKa 4.1Williams(2002)HB+
Human Pharmacokinetics
印花税如何计算Becau ceftazidime is not absorbed from the gastrointestinal tract it must be adminis-tered parenterally.It is widely distributed to body fluids and tissues and is excreted unchanged in urine.
Pharmacokinetic Properties
Value Units Prep.and
Route of
Admin.Reference Comments
Absorption
Bioavailability
Distribution Ceftazidime is widely distributed to body fluids and tissues.Penetration into
the cerebrospinal fluid is good with inflamed meninges.
Volume of Distribution0.23l/kg Balant et al
(1985)The volume of distribution of ceftazidime is incread in aged and burn patients.
Ceftazidime 2
一颗星是什么军衔Plasma Protein Binding<10%Physician’s
Desk
Reference
(2003) Metabolism
Plasma Half-Life 1.9hrs i.v.Physician’s
Desk
Reference
(2003)The plasma half-life is2hr administration and is prolonged if renal function is impaired.
Bio Half-Life
Clearance100ml/min Physician’s
Desk
Reference
(2003)
Renal clearance.
Routes of Elimination Approximately80–90%of an administered do of ceftazidime is excreted
unchanged in urine by glomerular filtration.
Targets-Pharmacodynamics
Ceftazidime is a bactericidal antibiotic that inhibits bacterial cell wall synthesis by binding to one or more penicillin binding proteins of actively dividing cells.It is also propod that cephalosporins decrea the availability of an inhibitor to murein hydrola(autolysin),an enzyme involved in cell division.
Target Name(s):
Penicillin binding proteins
Therapeutics
Ceftazidime is active against a wide range of gram-negative organisms,including Pudo-monas aeruginosa.Although ceftazidime is active in vitro against gram-positive bacteria,it is rarely ud for the infections.Ceftazidime is ud for the treatment of meningitis,lower respiratory infections,febrile neutropenic events,urinary tract infections,pelvic inflam-matory dia,and skin structure and skin infections.
Indications
Value Units Prep.and
Route of
Admin.Reference Comments
Pneumonia
Dosage500–2,000mg i.m.
every
8hrs Physician’s
Desk
Reference
(2003)
For pudomonal or vere,
life threatening infections
2g of ceftazidime should
be given i.v.every8hrs.
Dos must be reduced in
tho with renal
insufficiency bad on
creatinine clearance.
Intraabdominal Infection
Ceftazidime3
Dosage
2
热切的意思
g
i.v.every 8hrs
Physician’s Desk
Reference (2003)Dos must be reduced in tho with renal
insufficiency bad on creatinine clearance.Urinary Tract Infection Dosage 250–500自闭症孩子的特征
mg
i.m.
every 8–12hrs
Physician’s Desk
Reference (2003)
Complicated urinary tract infections should be
treated with higher dos and,possibly,a more frequent dosing interval.Dos must be reduced in tho with renal
insufficiency bad on creatinine clearance.Skin and Skin Structure,Mild Dosage 500–1,000mg
i.m.
every 8hrs水浒传读书笔记摘抄
Physician’s Desk
曾轶可狮子座Reference (2003)Dos must be reduced in tho with renal
insufficiency bad on creatinine clearance.Bone and Joint Infection Dosage 2G
i.v.every 12
hrs
Physician’s Desk
Reference (2003)Dos must be reduced in tho with renal
insufficiency bad on creatinine clearance.Meningitis Dosage 2
g
i.v.every
8hrs
Physician’s Desk
Reference (2003)Dos must be reduced in tho with renal
insufficiency bad on creatinine clearance.Infections,Pediatrics Dosage 30–50
mg/kg
i.v.every
8hrs
Physician’s Desk
Reference (2003)
Maximum of 6g/day.Dos must be reduced in tho with renal insufficiency bad on creatinine clearance.
Contraindications
Ceftazidime is contraindicated in patients with a history of allergic reactions to cephalo-sporin antibiotics.Ceftazidime should be avoided in tho with anaphylactic reactions to penicillins and should be ud with caution in patients with delayed hypernsitivity reactions such as rash,fever,or eosinophilia AHFS (2001).Adver Effects
Hypernsitivity reactions occur in approximately 5%or less of patients receiving cephalosporin antibiotics.The include urticaria,pruritis,rash,fever,eosinophilia,angioedema,hypotension,Stevens-Johnson Syndrome,erythema multiforme,toxic epi-dermal necrolysis,and exfoliative dermatitis.Positive direct and indirect antiglobulin (Coombs’)test have been reported in 3%or more of patients receiving cephalosporins.Rarely,cephalosporins cau neutropenia,thrombocytopenia,leukocytosis,granulocyto-sis,monocytosis,lymphocytopenia,basophilia,reversible leukopenia,aplastic anemia,pancytopenia,and hemolytic anemia.Transient increas in BUN and rum creatinine,renal
dysfunction and nephrotoxicity have occurred with cephalosporin u,as have transient increas in AST,ALT ,GGT ,and alkaline phosphota.Clostridium difficile colitis can occur with cephalosporin u AHFS (2001).
Ceftazidime
4
Agent-Agent Interactions
Agent Name Mode of Interaction
Aminoglycoside antibiotics Aminoglycoside ,gentamicin,tobramycin,amikacin).There is an incread risk of nephrotoxicity associated with the concurrent u of ceftazidime and aminoglycoside antibiotics.
Pre-Clinical Rearch Pharmacokinetics Potency
Value Units Organ/
Tissue
Prep.
and
Route of
Admin.
Cell
Line/
Type Effects
Exp.
End
Point Reference Comments
Rat
LD505800mg/kg i.v.Poisindex
(2003)
LD50>20g/Poisindex
(2003)
Mou
LD506300mg/kg i.v.Poisindex
(2003)
LD50>20g/Poisindex
(2003)
Rabbit
LD50>2g/kg i.v.Poisindex
(2003)
Journal Citations
Balant,L.,Dayer,P.,Auckenthaler,R.,1985.Clinical pharmacokinetics of third generation cephalosporins.
Clin.Pharmacokinet.,10,101–143.
Book Citations
Sweetman,S.,2003.Martindale:The Complete Drug Reference.Sweetman,S.(Ed.),Micromedex,
Electronic Version.Pharmaceutical Press,Greenwood Village,Colorado.
Williams,D.,2002.pKa Values for Some Drugs and Miscellaneous Organic Acids and Bas.Williams,D.A.,
Lemke,T.L.(Ed.),Foye’s Principles of Medicinal Chemistry,Edition5,p.1071,Lippincott Williams and
Wilkins,Philadelphia.
Physician’s Desk Reference,2003,Product Information.Murray,L.(Ed.),Physician’s Desk Reference,pp.
1533–1536,Thomson PDR,Montvale,New Jery.
AHFS,2001,Drug Monographs.McEvoy,G.(Ed.),American Hospital Formulary System,pp.128–253,
American Society of Health-System Pharmacists,Inc.,Bethesda,Maryland.
夜的笔顺Poisindex,2003,Poisindex System.Toll,L.L.,Hurlbut,K.M.(Ed.),Micromedex,Electronic Version.
Pharmaceutical Press,Greenwood Village,Colorado.
Ceftazidime5
