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
Cefalexin is well absorbed in the upper gastrointestinal tract, with an oral bioavailability approaching 100%. Cefalexin is not absorbed by the stomach but rather by the upper small intestine. Peak plasma concentrations in patients taking 250 mg of cefalexin are 7.7 mcg/mL, and in patients taking 500 mg, peak plasma concentrations are 12.3 mcg/mL. Over 90% of cefalexin is excreted in the urine via glomerular filtration and tubular secretion after 6 hours, with an average urinary recovery rate of 99.3%. Cefalexin is not excreted unchanged in the urine. 5.2–5.8 liters. The clearance rate in one subject was 376 ml/min. Less than 10% to 15% of the drug binds to plasma proteins, leading to a rapid decrease in plasma drug concentration… Over 90% of the drug is excreted unchanged in the urine within 6 hours, primarily via tubular secretion. ...Even in patients with impaired renal function, therapeutically effective concentrations can still be achieved in the urine. Cefalexin is well absorbed from the gastrointestinal tract. Peak plasma concentrations are reached approximately 1 hour after administration, with levels of approximately 9 μg/mL after oral administration of 250 mg and 18 μg/mL after oral administration of 500 mg. Food intake may delay absorption. Cefalexin is also excreted via bile. Absorption and excretion of cefalexin are impaired in newborns, with 24-hour urinary recovery rates ranging from 5% to 66% of the daily oral dose. For more complete data on absorption, distribution, and excretion of cefalexin (14 items in total), please visit the HSDB records page. Metabolites/Metabolites: Cefalexin is not metabolized in the body. Biological Half-Life: The half-life of cefalexin is 49.5 minutes on an empty stomach and 76.5 minutes after food, but these differences are not statistically significant. The results of this study differ. Less than 10% to 15% of the drug binds to plasma proteins, and plasma drug concentrations decline rapidly; the half-life of cefalexin is typically approximately 40 minutes. In rats, the average ratio of bone to serum concentration of cefalexin was 1:9 within 0.25–4 hours after oral administration. Despite the concentration differences, the half-life in bone and serum was similar. After administration of 1 g or 2 g of cefalexin, the time to peak concentration, elimination half-life, absorption half-life, and volume of distribution were similar. The half-life of cefalexin in the serum of adults with normal renal function is 0.5–1.2 hours. It has been reported that the half-life of this drug in neonatal serum is approximately 5 hours, and in children aged 3–12 months it is approximately 2.5 hours. In one study, the half-life of this drug in the serum of adults with a creatinine clearance of 9.2 mL/min was 7.7 hours, and in the serum of adults with a creatinine clearance of 4 mL/min it was 13.9 hours.

Interactions
Probenecid can effectively slow urinary clearance of cephalexin and prolong the duration of its systemic antibacterial activity. Cephalosporins may be affected by concomitant use with sulfinpyrazone. Reduced renal tubular secretion leads to higher serum drug concentrations and longer durations of action, thereby enhancing drug activity. Furosemide may enhance the nephrotoxicity of cephalosporins. /Cephalexins/ Hypoprothrombinemia caused by high doses of salicylates and/or cephalosporins, as well as the risk of gastrointestinal ulcers or bleeding associated with nonsteroidal anti-inflammatory drugs (NSAIDs), salicylates, or sulfinpyrazone, may increase the risk of bleeding. Cephalosporins For more complete data on the interactions of ceftriaxone (6 drugs in total), please visit the HSDB record page.

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Non-human toxicity values
Mice oral LD50: 1.6-4.5 g/kg/monohydrate/
Mice intraperitoneal LD50: 0.4-1.3 g/kg/monohydrate/
Rat oral LD50: >5.0 g/kg/monohydrate/
Rat intraperitoneal LD50: >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

Cephalexin's antibacterial spectrum is similar to that of penicillin…Penicillin G is generally more effective against cocci and Gram-positive bacilli. …Most penicillinases do not affect cephalexin…
Cephalexins are highly effective against a wide range of mild to severe infections caused by Gram-positive and Gram-negative bacteria.
Cephalexins are…the first-line treatment for Klebsiella pneumoniae infections. …They are…important adjunctive therapies and are often used as an alternative to penicillin.
For more complete data on the therapeutic uses of cephalexin (9 types), please visit the HSDB record page.
Drug Warnings

When renal function is impaired, the doctor must adjust the dosage or dosing interval.
Cephalexins should not be used to treat bacterial meningitis. This applies to all pathogenic microorganisms. …Cephalexins have poor permeability in cerebrospinal fluid. Cephalosporins
Enterococcal infections are generally unaffected by these antibiotics…Cephalosporins cannot cure enterococcal endocarditis, even when used concurrently with gentamicin or streptomycin. Cephalosporins
Enterobacterial (aerobic) infections are often resistant to these antibiotics. Cephalosporins
For more complete data on drug warnings for cephalexin (20 in total), please visit the HSDB records page.

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Pharmacodynamics
Cephalexin (also known as cephalosporin) is a first-generation cephalosporin antibiotic. It is one of the most commonly used antibiotics and is often used to treat superficial infections caused by minor wounds or lacerations. It is effective against most Gram-positive bacteria by inhibiting the cross-linking reaction between N-acetylmuramic acid 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。