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

头孢氨苄一水合物 (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（Cefalexin）一水合物可抑制多种革兰氏阳性和革兰氏阴性微生物； tarda、Alcaligenes sp 和 Proteus rettgeri 的 MIC 值分别为 2、2、2、2、4、4.4 和 5.7 μg/mL[2]。

头孢氨苄一水合物（0-50 mg/kg；口服；3.5 小时）的抗菌活性已在感染微生物的雄性 Swiss-Webster 小鼠中得到证实 [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.

Absorption
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. The peak plasma concentration in patients taking 250 mg of cefalexin is 7.7 mcg/mL, and in patients taking 500 mg, the peak plasma concentration is 12.3 mcg/mL.
Excretion
Cefalexin is excreted in the urine after 6 hours via glomerular filtration and tubular secretion. Over 90% of cefalexin is excreted in the urine, with an average urinary recovery rate of 99.3%. Cefalexin is excreted unchanged in the urine.
Volume of Distribution
5.2–5.8 L.
Clearance
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 decline in plasma drug concentration…Over 90% of the drug is excreted unchanged in the urine within 6 hours, primarily through renal tubular secretion. …Even in patients with impaired renal function, therapeutically effective concentrations can still be achieved in the urine.
Cephalexin…is readily absorbed from the gastrointestinal tract. After oral administration of 250 mg and 500 mg, peak plasma drug concentrations are approximately 9 μg/mL and 18 μg/mL, respectively, reached approximately 1 hour after administration. Food intake may delay absorption.
Absorption and excretion of cephalexin are impaired in newborns, with 24-hour urinary recovery rates ranging from 5% to 66% of the daily oral dose.

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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 on an empty stomach and 76.5 minutes after eating, but the difference between these two time points was not statistically significant in this study. The half-life of cephalexin in the serum of adults with normal renal function is 0.5–1.2 hours. It has been reported that the half-life of cephalexin in the serum of newborns is approximately 5 hours, and in children aged 3–12 months, it is approximately 2.5 hours. One study showed that the half-life in the serum of adults with a creatinine clearance of 9.2 ml/min is 7.7 hours, and in adults with a creatinine clearance of 4 ml/min, it is 13.9 hours.

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Protein Binding
The binding rate of cephalexin to serum proteins (including serum albumin) is 10–15%.

Effects During Pregnancy and Lactation
◉ Overview of Lactation Use
Limited information suggests that low concentrations of cephalexin in breast milk after maternal administration generally do not adversely affect breastfed infants. Cephalexin is an alternative treatment for mastitis. There are reports that cephalosporins occasionally disrupt the infant's gut microbiota, leading to diarrhea or thrush, but these effects have not been fully assessed. There has been one rare case of a severe allergic reaction in an infant who had previously received intravenous cefazolin, and whose mother began taking cephalexin while breastfeeding. It is safe for breastfeeding women to take cephalexin.
◉ Effects on Breastfed Infants
In a prospective follow-up study, seven breastfeeding mothers reported taking cephalexin (dosage not specified). Two of these mothers reported their infants developing diarrhea. No rashes or candidiasis were reported in infants exposed to cephalexin.
A prospective controlled study surveyed mothers who called the information service center about adverse reactions in their breastfed infants. One in 11 infants exposed to cephalexin reported diarrhea while their mothers were receiving cephalexin treatment.
One woman received intravenous cefotaxime 1 gram every 6 hours for 3 days. Her breastfed infant developed green, loose stools, severe diarrhea, discomfort, and crying. The mother's regimen was subsequently changed to oral cephalexin 500 mg plus oral probenecid 500 mg four times daily for 16 days. During this period, the infant continued to have diarrhea. The authors believe the diarrhea may be related to cephalexin in the breast milk.
A 4-month-old infant received intravenous cefazolin for a urinary tract infection. Nine days after discharge and discontinuation of cefazolin, the infant developed a vesicular rash covering most of the body and was diagnosed with toxic epidermal necrolysis (TEN). The infant was breastfed by the mother (the extent of breastfeeding was not specified), who had started taking cephalexin two days before the onset of symptoms. A lymphocyte transformation test performed 4 weeks after the end of TEN treatment revealed that the infant was allergic to both cefazolin and cephalexin. The infant's reaction may have been due to an initial allergic reaction to cefazolin, followed by a cross-reaction with cefazolin in breast milk.
◉ Effects on breastfeeding and breast milk
As of the revision date, no relevant published information was found.

[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.

Cephalexin monohydrate is the hydrated form of cephalexin, composed of equimolar amounts of cephalexin and its hydrate. It is an antibacterial drug. It contains cephalexin. It is a semi-synthetic cephalosporin antibiotic with antibacterial activity similar to cefadroxil or cefotaxime, but slightly weaker. It is effective against both Gram-positive and Gram-negative bacteria. See also: Cephalexin (note moved to).

C16H19N3O5S

365.404

383.07

C, 52.59; H, 5.24; N, 11.50; O, 21.89; S, 8.77

23325-78-2

Cephalexin;15686-71-2;Cephalexin hydrochloride;59695-59-9;Cephalexin-d5 monohydrate;Cephalexin hydrochloride monohydrate;105879-42-3;Cephalexin (lysine);53950-14-4

62921

White to off-white solid powder

1.5g/cm3

727.4ºC at 760 mmHg

393.7ºC

3.27E-22mmHg at 25°C

154 ° (C=0.5, H2O)

1.409

147.26

4

7

4

25

600

3

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

AVGYWQBCYZHHPN-CYJZLJNKSA-N

InChI=1S/C16H17N3O4S.H2O/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);1H2/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;hydrate

Cefibacter; Cefalival; Cephalexin monohydrate; 23325-78-2; Cephalexin hydrate; cefalexin monohydrate; cefalexin hydrate; Cephalexin (monohydrate); Keforal; Novolexin; Cephalexin hydrate

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)

DMSO : ~6.67 mg/mL (~18.25 mM)
H2O : ~2 mg/mL (~5.47 mM)

配方 1 中的溶解度: ≥ 0.67 mg/mL (1.83 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 6.7 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 0.67 mg/mL (1.83 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 6.7mg/mL澄清的DMSO储备液加入到900μL 20％SBE-β-CD生理盐水中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 0.67 mg/mL (1.83 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 6.7 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 8.33 mg/mL (22.80 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶 (<60°C).

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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。