Bacterial cell wall synthesis; penicillin binding proteins (PBPs); cephalosporin antibiotic

头孢氨苄 (10 μg/mL) 可使一种称为青霉素结合蛋白 (PBP) 的酶失活，该酶会干扰聚合物肽聚糖 (PG) 的合成 [1]。头孢氨苄可抑制多种革兰氏阳性和革兰氏阴性微生物，对雷氏变形杆菌的 MIC 值分别为 2、2、2、2、4、4.4 和 5.7 μg/mL [2]。

头孢氨苄（0-50 mg/kg；口服；3.5 小时）对感染微生物的雄性 Swiss-Webster 小鼠表现出抗菌作用 [2]。

青霉素和相关的β -内酰胺构成了我们最古老和最广泛使用的抗生素疗法之一。人们早就知道，这些药物的靶点是一种叫做青霉素结合蛋白(PBPs)的酶，这种酶负责构建细菌细胞壁。研究了靶抑制的下游后果，以及它们如何导致这些重要药物的致命作用，我们证明了β -内酰胺不仅仅是像通常认为的那样抑制PBPs。相反，它们诱导目标生物合成机制发生毒性故障，涉及细胞壁合成和降解的无效循环，从而耗尽细胞资源并增强其杀伤活性。这种作用模式的表征还揭示了细胞壁基质中裂解键的酶的质量控制功能。因此，这些结果提供了对细胞壁组装机制的深入了解，并建议如何最好地干预未来抗生素开发的过程。[1]

Animal/Disease Models: Bacterially infected male Swiss-Webster mice [2]
Doses: 0-50 mg/kg
Route of Administration: po (po (oral gavage)) 3.5 hrs (hrs (hours))
Experimental Results: Against Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus aureus and several Antimicrobial activity against Gram-negative bacteria in mice.

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Cefadroxil is a new semisynthetic cephalosporin with a broad antibacterial spectrum and a high chemotherapeutic potential when administered orally. The inhibitory activity of this compound was similar to that of cephalexin and cephradine when tested against 602 clinical isolates on Mueller-Hinton medium. In the oral treatment of experimental infections of mice, cefadroxil was more effective than cephalexin against Streptococcus pyogenes, and comparably effective against Streptococcus pneumoniae, Staphylococcus aureus, and several gram-negative species. Administered orally to mice, at doses ranging from 25 to 100 mg/kg, cefadroxil attained peak concentrations in the blood similar to those of cephalexin. At a dose of 200 mg/kg, however, higher peak levels were noted with cefadroxil than with cephalexin. In regard to other properties which were investigated, the behavior of cefadroxil compared favorably to that of cephalexin.[2]

Absorption, Distribution and Excretion
Well absorbed from the upper gastrointestinal tract with nearly 100% oral bioavailability. Cephalexin is not absorbed in the stomach but is absorbed in the upper intestine. Patients taking 250mg of cephalexin reach a maximum plasma concentration of 7.7mcg/mL and patients taking 500mg reach 12.3mcg/mL.
Cephalexin is over 90% excreted in the urine after 6 hours by glomerular filtration and tubular secretion with a mean urinary recovery of 99.3%. Cephalexin is unchanged in the urine.
5.2-5.8L.
Clearance from one subject was 376mL/min.
LESS THAN 10 TO 15%...IS BOUND TO PLASMA PROTEIN, & PLASMA DRUG CONCN FALL RAPIDLY... MORE THAN 90%...IS EXCRETED UNALTERED IN URINE WITHIN 6 HR, PRIMARILY BY RENAL TUBULAR SECRETION. ...THERAPEUTICALLY EFFECTIVE CONCN ARE STILL ACHIEVED IN URINE OF PT WITH DECR RENAL FUNCTION.
CEPHALEXIN...IS WELL ABSORBED FROM GI TRACT. PEAK PLASMA CONCN, REACHED @ ABOUT 1 HR AFTER INGESTION OF DRUG, ARE APPROX 9 & 18 UG/ML AFTER ORAL DOSES OF 250 & 500 MG, RESPECTIVELY. INGESTION OF FOOD MAY DELAY ABSORPTION.
CEPHALEXIN IS ALSO EXCRETED INTO BILE.
BOTH ABSORPTION & EXCRETION OF CEPHALEXIN ARE IMPAIRED IN NEW-BORN INFANTS, WHERE 24-HR URINARY RECOVERY OF ANTIBIOTIC ACCOUNTED FOR 5-66% OF DAILY ORAL DOSE.
For more Absorption, Distribution and Excretion (Complete) data for CEPHALEXIN (14 total), please visit the HSDB record page.

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Metabolism / Metabolites
Cephalexin is not metabolized in the body.

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Biological Half-Life
The half life of cephalexin is 49.5 minutes in a fasted state and 76.5 minutes with food though these times were not significantly different in the study.
LESS THAN 10 TO 15%...IS BOUND TO PLASMA PROTEIN, & PLASMA DRUG CONCN FALL RAPIDLY, T/2 OF CEPHALEXIN NORMALLY BEING ABOUT 40 MIN.
/IN RATS/ RATIOS OF BONE TO SERUM CONCN AVG...1:9 FOR CEPHALEXIN DURING 0.25-4 HR AFTER /ORAL/ DOSING. DESPITE DIFFERENCES IN CONCN; T/2 IN BONE & SERUM WERE SIMILAR.
PEAK TIME, T/2 OF ELIMINATION, T/2 OF ABSORPTION, & VOL OF DISTRIBUTION WERE ALL SIMILAR FOLOWING ADMIN OF EITHER 1 OR 2 G OF CEPHALEXIN.
The serum half-life of cephalexin is 0.5-1.2 hr in adults with normal renal function. The serum half-life of the drug is reported to be about 5 hr in neonates and 2.5 hr in children 3-12 mo of age. In one study, the serum half-life was 7.7 hr in adults with creatinine clearances of 9.2 ml/min and 13.9 hr in adults with creatinine clearances of 4 ml/min.

Interactions
PROBENECID IS EFFECTIVE IN SLOWING URINARY CLEARANCE & ENHANCING DURATION OF SYSTEMIC ANTIMICROBIAL ACTIVITY /OF CEPHALEXIN/.
...CEPHALOSPORINS...MAY BE AFFECTED BY CONCURRENT USE OF...SULFINPYRAZONE. DIMINISHED TUBULAR SECRETION...RESULT IN HIGHER & MORE SUSTAINED SERUM LEVELS & HENCE, INTENSIFICATION OF DRUG ACTIVITY. /CEPHALOSPORINS/
FUROSEMIDE MAY ENHANCE NEPHROTOXICITY OF CEPHALOSPORINS. /CEPHALOSPORINS/
Hypoprothrombinemia induced by large doses of salicylates and/or cephalosporins, and the gastrointestinal ulcerative or hemorrhagic potential of nonsteroidal anti-inflammatory drugs (NSAIDs), salicylates, or sulfinpyrazone may increase the risk of hemorrhage. /Cephalosporins/
For more Interactions (Complete) data for CEPHALEXIN (6 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 MOUSE ORAL 1.6-4.5 G/KG /MONOHYDRATE/
LD50 MOUSE INTRAPERITONEAL 0.4-1.3 G/KG /MONOHYDRATE/
LD50 RAT ORAL GREATER THAN 5.0 G/KG /MONOHYDRATE/
LD50 RAT INTRAPERITONEAL GREATER THAN 3.7 G/KG /MONOHYDRATE/

[1]. Beta-lactam antibiotics induce a lethal malfunctioning of the bacterial cell wall synthesis machinery. Cell. 2014 Dec 4;159(6):1300-11.

[2]. Cefadroxil, a new broad-spectrum cephalosporin. Antimicrob Agents Chemother. 1977 Feb;11(2):324-30.

Therapeutic Uses
Cephalosporins
/CEPHALEXIN/ HAS ANTIBACTERIAL SPECTRUM SIMILAR TO THAT OF PENICILLINS... AGAINST COCCI & GRAM-POSITIVE BACILLI, PENICILLIN G IS USUALLY MORE EFFECTIVE. ...MOST PENICILLINASES DO NOT AFFECT CEPHALEXIN...
...CEPHALOSPORINS ARE HIGHLY EFFECTIVE IN THERAPY OF VARIETY OF MILD-TO-SEVERE INFECTIONS DUE TO BOTH GRAM-POSITIVE & GRAM-NEGATIVE MICROORGANISMS. /CEPHALOSPORINS/
...CEPHALOSPORIN IS...DRUG OF 1ST CHOICE...FOR KLEBSIELLA INFECTIONS. ... THEY ARE...VALUABLE SECONDARY AGENTS, & THEY FREQUENTLY APPEAR AS ALTERNATIVE CHOICES TO PENICILLIN. /CEPHALOSPORINS/
For more Therapeutic Uses (Complete) data for CEPHALEXIN (9 total), please visit the HSDB record page.

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Drug Warnings
PHYSICIAN MUST ALTER EITHER DRUG DOSAGE OR INTERVAL BETWEEN DOSES WHEN RENAL FUNCTION IS IMPAIRED.
CEPHALOSPORINS SHOULD NOT BE USED TO TREAT BACTERIAL MENINGITIS. THIS IS TRUE FOR ALL CAUSATIVE MICROORGANISMS. ...PENETRATION OF CEPHALOSPORINS INTO CSF IS POOR. /CEPHALOSPORINS/
INFECTIONS DUE TO ENTEROCOCCI ARE USUALLY UNAFFECTED BY THESE CMPD... ENTEROCOCCAL ENDOCARDITIS CANNOT BE CURED WITH CEPHALOSPORIN EVEN WHEN IT IS GIVEN CONCURRENTLY WITH GENTAMICIN OR STREPTOMYCIN. /CEPHALOSPORINS/
ENTEROBACTER (AEROBACTER) INFECTIONS ARE, AS A RULE, RESISTANT TO THESE CMPD. /CEPHALOSPORINS/
For more Drug Warnings (Complete) data for CEPHALEXIN (20 total), please visit the HSDB record page.

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Pharmacodynamics
Cephalexin (also called Cefalexin) is a first generation cephalosporin antibiotic. It is one of the most widely prescribed antibiotics, often used for the treatment of superficial infections that result as complications of minor wounds or lacerations. It is effective against most gram-positive bacteria through its inihibition of the cross linking reaction between N-acetyl muramicacid and N-acetylglucosamine in the cell wall, leading to cell lysis.

C16H17N3O4S

347.89

347.093

C, 55.32; H, 4.93; N, 12.10; O, 18.42; S, 9.23

15686-71-2

Cephalexin hydrochloride;59695-59-9;Cephalexin monohydrate;23325-78-2;Cephalexin hydrochloride monohydrate;105879-42-3;Cephalexin (lysine);53950-14-4;Cephalexin-d5;2101505-56-8; 15686-71-2 (free); 38932-40-0 (sodium)

27447

White to light yellow solid powder

1.5±0.1 g/cm3

727.4±60.0 °C at 760 mmHg

196-198°C

393.7±32.9 °C

0.0±2.5 mmHg at 25°C

1.700

0.65

138.03

3

6

4

24

600

3

CC1=C(N2[C@@H]([C@@H](C2=O)NC(=O)[C@@H](C3=CC=CC=C3)N)SC1)C(=O)O

ZAIPMKNFIOOWCQ-UEKVPHQBSA-N

InChI=1S/C16H17N3O4S/c1-8-7-24-15-11(14(21)19(15)12(8)16(22)23)18-13(20)10(17)9-5-3-2-4-6-9/h2-6,10-11,15H,7,17H2,1H3,(H,18,20)(H,22,23)/t10-,11-,15-/m1/s1

(6R,7R)-7-[[(2R)-2-amino-2-phenylacetyl]amino]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Cephacillin; Cefalexin; Keflex; Cepexin; Carnosporin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~10 mg/mL (~28.79 mM)

配方 1 中的溶解度: 25 mg/mL (71.97 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 通过加热和超声助溶。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。