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
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.

Route of Elimination
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.

Volume of Distribution
5.2-5.8L.

Clearance
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.

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.

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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. 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.

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Protein Binding
Cephalexin is 10-15% bound to serum proteins including serum albumin.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Limited information indicates that maternal cephalexin produces low levels in milk that are usually not expected to cause adverse effects in breastfed infants. Cephalexin is an alternative for the treatment of mastitis. Occasionally disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush have been reported with cephalosporins, but these effects have not been adequately evaluated. A rare case of a severe allergic reaction occurred in an infant previously exposed to intravenous cefazolin whose mother began taking cephalexin while breastfeeding. Cephalexin is acceptable in nursing mothers.
◉ Effects in Breastfed Infants
In a prospective follow-up study, 7 nursing mothers reported taking cephalexin (dosage not specified). Two mothers reported diarrhea in their infants. No rashes or candidiasis were reported among the exposed infants.
A prospective, controlled study asked mothers who called an information service about adverse reactions experience by their breastfed infants. One of 11 cephalexin-exposed infants reportedly developed diarrhea during maternal cephalexin therapy.
A woman received intravenous cephalothin 1 g every 6 hours for 3 days. Her breastfed infant had a green liquid stool, severe diarrhea, discomfort and crying. The mother's drug regimen was then changed to oral cephalexin 500 mg plus oral probenecid 500 mg 4 times daily for another 16 days. The infant continued to have diarrhea during this time. The authors rated the diarrhea as probably related to cephalexin in milk.
A 4-month-old infant was treated with intravenous cefazolin for a urinary tract infection. Nine days after being discharged and cefazolin discontinuation, the infant developed a blistering rash over most of the body that was diagnosed as toxic epidermal necrolysis (TEN). The infant was being breastfed (extent unspecified) by his mother who had begun cephalexin 2 days prior to the onset of symptoms. A lymphocyte transformation test performed 4 weeks after treatment for TEN was completed found sensitization to both cefazolin and cephalexin. The infant's reaction was probably caused by cephalexin in breastmilk after initial sensitization and subsequent cross-reaction to cefazolin.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

[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 a hydrate of cephalexin consisting of equimolar amounts of hydrate and cephalexin. It has a role as an antibacterial drug. It contains a cephalexin.
A semisynthetic cephalosporin antibiotic with antimicrobial activity similar to that of CEPHALORIDINE or CEPHALOTHIN, but somewhat less potent. It is effective against both gram-positive and gram-negative organisms.
See also: Cephalexin (annotation 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。