![Ampicillin [D-(-)-α-Aminobenzylpenicillin)] 69-53-4](/picture/img/Ampicillin [D-(-)-α-Aminobenzylpenicillin)] Chemical Structure.png)
Ampicillin [D-(-)-α-Aminobenzylpenicillin)] is a potent broad-spectrum beta-lactam antibiotic widely used to prevent and treat a number of bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, salmonellosis, and endocarditis. It may also be used to prevent group B streptococcal infection in newborns. It is used by mouth, by injection into a muscle, or intravenously. Like all antibiotics, it is not useful for the treatment of viral infections.
Physicochemical Properties
| Molecular Formula | C16H19N3O4S |
| Molecular Weight | 349.40476 |
| Exact Mass | 349.109 |
| Elemental Analysis | C, 55.00; H, 5.48; N, 12.03; O, 18.32; S, 9.18 |
| CAS # | 69-53-4 |
| Related CAS # | Ampicillin sodium;69-52-3;Ampicillin trihydrate;7177-48-2;Ampicillin-d5;1426173-65-0; Ampicillin;69-53-4;Ampicillin trihydrate;7177-48-2; 69-53-4 (free acid); 23277-71-6 (potassium); 114977-84-3 (trimer trisodium) ; 69-52-3 (sodium); 7490-86-0 (hemisulfate); 33276-75-4 (benzathine); 119229-01-5 (embonate); 40688-84-4 (HCl) |
| PubChem CID | 6249 |
| Appearance | White to off-white solid powder |
| Density | 1.6±0.1 g/cm3 |
| Boiling Point | 644.5±65.0 °C at 760 mmHg |
| Melting Point | 198-200 °C (dec.)(lit.) |
| Flash Point | 343.6±34.3 °C |
| Vapour Pressure | 0.0±2.0 mmHg at 25°C |
| Index of Refraction | 1.724 |
| LogP | 1.65 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 24 |
| Complexity | 562 |
| Defined Atom Stereocenter Count | 4 |
| SMILES | OC([C@@H]1N(C2=O)[C@]([C@@H]2NC([C@@H](C3=CC=CC=C3)N)=O)([H])SC1(C)C)=O |
| InChi Key | AVKUERGKIZMTKX-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C16H19N3O4S/c1-16(2)11(15(22)23)19-13(21)10(14(19)24-16)18-12(20)9(17)8-6-4-3-5-7-8/h3-7,9-11,14H,17H2,1-2H3,(H,18,20)(H,22,23) |
| Chemical Name | (2S,5R,6R)-6-[[(2R)-2-amino-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid |
| Synonyms | Aminobenzylpenicillin; 69-53-4; Ampicillin; Aminobenzylpenicillin; Ampicillin acid; Tokiocillin; Omnipen; Amcill; Ampicillin Anhydrous; Ampicillin acid; Principen; Amcill; |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | β-lactam; cell wall synthesis |
| ln Vitro | Ampicillin has a dose-dependent effect on swine-derived E. Coli growth inhibition. Ampicillin's effective inhibitory concentration was 2.5 uG/mL[1]. |
| ln Vivo | When hemorrhagic enteritis strikes an 11-week-old pig, ampicillin works wonders to relieve the symptoms[1]. Maximum concentrations of ampicillin are twice as high in bile as they are in serum. After an oral dosage, the peak concentration of ampicillin in portal blood is twice as high as in peripheral blood[2]. Neuroprotection against brain damage caused by ischemia-reperfusion is offered by ampicillin. Ampicillin raises the level of GLT-1 expression while decreasing MMP activity. After global forebrain ischemia, pretreatment with ampicillin dramatically lowers medial hippocampal cell death[3]. |
| Enzyme Assay | SENSITIVITY TESTING[1] A set of 5 replicate tubes at each concentration of the antibiotic were inoculated with one drop each of an 18 hour growth of the test culture. The inoculated tubes were incubated at 37°C. for 6 hours, after which further growth was stopped by mixing formalin at 0.5% final concentration. Growth of cultures was recorded as the optical density, employing a Fisher Electrophotometer3 with a 525 m.u. filter. |
| Cell Assay | The in vitro susceptibility of 103 cultures of E. coli isolated from scouring and nonscouring pigs, and four cultures of Salmonella isolated from a case of necrotic enteritis was tested against Ampicillin contained in nutrient broth at concentrations of 0, 0.1, 1.0 and 5.0 uG per ml. of the medium. All but three cultures of E. coli were found to be susceptible to 5.0 uG/ml., all Salmonella isolates were also susceptible to this concentration of the antibiotic. Susceptibility of E. coli was also tested by plating dilutions of fecal samples obtained from either a scouring or a nonscouring pig, with E.M.B. agar containing 0, 0.1, 1.0, 2.5, 5.0 and 10.0 uG Ampicillin per ml. of the medium. No difference in the growth of E. coli was observed at 0, 0.1 and 1.0 uG concentrations. The three higher concentrations of the antibiotic inhibited the growth of E. coli proportional to the amount of Ampicillin in each concentration. Ampicillin proved very effective in alleviating the symptoms of hemorrhagic enteritis in a 11-week old pig. The disappearance of scours was associated with the replacement of the previously existing sero-biotypes of fecal E. coliwith another aberrant type of E.coli which produced H2S. No Ampicillin resistant strains of E. coli emerged following treatment of the animal with this antibiotic.[1] |
| Animal Protocol | Mice: Normal saline is used to dissolve ampicillin. After receiving halothane anesthesia, male C57BL/6 mice had their common carotid arteries blocked bilaterally for 40 minutes. Penicillin G (6,000 U/kg or 20,000 U/kg, intraperitoneally [i.p.]) or ampicillin (200 mg/kg) was given intraperitoneally (i.p.) every day for five days prior to transient forebrain ischemia. The same volume and timing of saline administration were used for the control animals[3]. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Ampicillin is excreted largely unchanged in the urine. INTAKE OF FOOD PRIOR TO INGESTION OF AMPICILLIN RESULTS IN LESS COMPLETE ABSORPTION. ... /IT/ APPEARS IN BILE, UNDERGOES ENTEROHEPATIC CIRCULATION & IS EXCRETED IN...FECES. BILIARY CONCN...DEPENDENT ON INTEGRITY OF GALLBLADDER & ITS DUCTS. Ampicillin is distributed to liver, bile, muscle, kidney, crop, and fat following absorption from the GI or injection site. Ampicillin has been used therapeutically and prophylactically for avian salmonellosis with promising results. ... Ampicillin is excreted in bile. Anhydrous ampicillin and ampicillin trihydrate are generally stable in the presence of acidic gastric secretions, and 30-55% of an oral dose of the drugs is absorbed from the GI tract in fasting adults. Although peak serum concn may occur as soon as 1 hr after administration, the maximum serum concn is usually attained in approx 2 hr. Two hr after oral administration of 250 mg of ampicillin in fasting individuals, average peak serum concn of 1.8-2.9 ug/ml are attained. A 500-mg oral dose results in average peak serum concn of 3-6 ug/ml. Concn of the antibiotic in serum are less than 1 ug/ml 6 hr after a 500-mg oral dose. For more Absorption, Distribution and Excretion (Complete) data for AMPICILLIN (16 total), please visit the HSDB record page. Metabolism / Metabolites AMPICILLIN IS DEGRADED BY PENICILLINASE... YIELDS ALPHA-AMINOBENZYLPENICILLOIC ACID IN BACILLUS, IN PENICILLIUM, AND L-PHENYLGLYCINE IN ESCHERICHIA. /FROM TABLE/ Healthy subjects metabolize about 20% of a given dose (250-500 mg) of ampicillin. Within 12 hr, 7% of the total dose is excreted as metabolites in urine ... Ampicillin is metabolized to 5R,6R-penicilloic acid and 5S,6R-penicilloic acid ... and to piperazine-2,5-dione after oral intake ... Other, unidentified metabolites have been reported ... . Biological Half-Life The half-life of all aminopenicillins is approximately 60-90 minutes. Following ip injection ... the serum half-life /of ampicillin/ was estimated to be 27 min ... . ... /ampicillin's/ plasma half-time is usually 1-2 hr ... but is longer in elderly people ... In patients with renal failure, the half-time was as long as 20 hr ... . |
| Toxicity/Toxicokinetics |
Hepatotoxicity Rare instances of idiosyncratic liver injury have been reported in persons receiving the aminopenicillins. The incidence is far lower with ampicillin than occurs with amoxicillin, occurring probably in less than 1 in 100,000 exposed persons. Cases are characterized by a short latency period of a few days to as long as two weeks. The onset of liver injury can occur after the antibiotic is stopped. The serum enzyme pattern associated with aminopenicillin liver injury has included a hepatocellular pattern with marked elevations in ALT and AST, and minimal elevations in alkaline phosphatase and rapid recovery after withdrawal. In addition, cholestatic forms of hepatic injury with marked alkaline phosphatase elevations (as also seen with penicillin-induced liver injury) have also been described, some of which have been associated with prolonged cholestasis and, rarely, with vanishing bile duct syndrome. The onset of hepatic injury may be accompanied by skin rash, toxic epidermal necrolysis or Stevens Johnson syndrome. Autoantibodies are uncommon. Likelihood score: C (probable but rare cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Substantial information indicates that ampicillin produces low levels in milk that are not expected to cause adverse effects in breastfed infants. Occasionally disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush have been reported with penicillins, but these effects have not been adequately evaluated. Ampicillin is acceptable in nursing mothers. ◉ Effects in Breastfed Infants An uncontrolled observation of the breastfed infants of mothers taking ampicillin noted a seeming increase in cases of diarrhea and candidiasis that was attributed to ampicillin in breastmilk. In a prospective follow-up study, 5 nursing mothers reported taking ampicillin (dosage unspecified). One mother reported diarrhea in her infant. No rashes or candidiasis were reported among the exposed infants. A small, controlled, prospective study had mothers monitor their infants for signs of adverse effects (furring of the tongue, feeding difficulties, changes in stool frequency and consistency, diaper rash, and skin rash). Weight change and the development of jaundice were also recorded. No statistical differences in these parameters were found between the infants of the control mothers and those of mothers taking ampicillin. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Interactions ...AMPICILLIN...MIXED IN VITRO WITH GENTAMICIN.../FOR PROLONGED PERIODS/ CAUSE LOSS OF GENTAMICIN ANTIMICROBIAL ACTIVITY. CONCURRENT ADMIN OF PENICILLIN & PROBENECID RESULTS IN HIGHER & MORE SUSTAINED SERUM ANTIBIOTIC LEVELS. /AMPICILLIN HAS BEEN SHOWN TO INTERACT IN SIMILAR MANNER/. /GENTAMICIN/ RELATED DRUGS...KANAMYCIN, NEOMYCIN & TOBRAMYCIN MAY INTERACT...WITH CARBENICILLIN. /CARBENICILLIN/ LIMITED...DATA INDICATE THAT ASPIRIN, IN LARGE DOSES, INCR SERUM LEVEL & HALF-LIFE OF PENICILLIN WHEN...GIVEN CONCURRENTLY. ALTHOUGH CONCURRENT USE OF HIGH DOSES OF ASPIRIN HAS BEEN SUGGESTED TO INCR CLINICAL BENEFITS OF PENICILLIN, POSSIBLE TOXICITIES DUE TO HIGH-DOSE ASPIRIN ADMIN DISCOURAGE SUCH THERAPY. /PENICILLIN/ For more Interactions (Complete) data for AMPICILLIN (21 total), please visit the HSDB record page. Non-Human Toxicity Values LD50 Rat oral 10 g/kg bw LD50 Mouse oral 15.2 g/kg bw LD50 Rat ip, 1 day old, 3300 mg/kg bw LD50 Rat ip, 83 day old, 4500 mg/kg bw |
| References |
[1]. Effect of Ampicillin on E. Coli of Swine Origin. Can J Comp Med Vet Sci. 1963 Sep;27(9):223-7. [2]. Ampicillin in portal and peripheral blood and bile after oral administration of ampicillin andpivampicillin. Eur J Clin Pharmacol. 1974;7(2):133-5. [3]. The neuroprotective mechanism of ampicillin in a mouse model of transient forebrain ischemia. Korean J Physiol Pharmacol. 2016 Mar;20(2):185-92. |
| Additional Infomation |
Ampicillin is a penicillin in which the substituent at position 6 of the penam ring is a 2-amino-2-phenylacetamido group. It has a role as an antibacterial drug. It is a penicillin, a penicillin allergen and a beta-lactam antibiotic. It is a conjugate acid of an ampicillin(1-). Ampicillin is a semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Ampicillin is a Penicillin-class Antibacterial. Ampicillin has been reported in Microsphaeropsis arundinis, Aspergillus banksianus, and other organisms with data available. Ampicillin is a broad-spectrum, semi-synthetic, beta-lactam penicillin antibiotic with bactericidal activity. Ampicillin binds to and inactivates penicillin-binding proteins (PBP) located on the inner membrane of the bacterial cell wall. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This interrupts bacterial cell wall synthesis and results in the weakening of the bacterial cell wall and causes cell lysis. Ampicillin is stable against hydrolysis by a variety of beta-lactamases, therefore, can be used in wide range of gram-positive and -negative infections. Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Drug Indication For treatment of infection (Respiratory, GI, UTI and meningitis) due to E. coli, P. mirabilis, enterococci, Shigella, S. typhosa and other Salmonella, nonpenicillinase-producing N. gononhoeae, H. influenzae, staphylococci, streptococci including streptoc Mechanism of Action By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, Ampicillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that Ampicillin interferes with an autolysin inhibitor. SINCE PENICILLIN HAS NO EFFECT ON EXISTING CELL WALLS, BACTERIA MUST BE MULTIPLYING FOR BACTERICIDAL ACTION OF PENICILLIN TO BE MANIFEST. /PENICILLINS/ The penicillins and their metabolites are potent immunogens because of their ability to combine with proteins and act as haptens for acute antibody-mediated reactions. The most frequent (about 95 percent) or "major" determinant of penicillin allergy is the penicilloyl determinant produced by opening the beta-lactam ring of the penicillin. This allows linkage of the penicillin to protein at the amide group. "Minor" determinants (less frequent) are the other metabolites formed, including native penicillin and penicilloic acids. /Penicillins/ Bactericidal; inhibit bacterial cell wall synthesis. Action is dependent on the ability of penicillins to reach and bind penicillin binding proteins located on the inner membrane of the bacterial cell wall. Penicillin binding proteins (which include transpeptidases, carboxypeptidases, and endopeptidases) are enzymes that are involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Penicillins bind to, and inactivate, penicillin binding proteins, resulting in the weakening of the bacterial cell wall and lysis. /Penicillins/ Therapeutic Uses Penicillins FOR MILD TO MODERATELY SEVERE DISEASE, ORAL...ADULTS...1-4 G/DAY, DIVIDED INTO EQUAL PORTIONS...EVERY 6 HR. FOR SEVERE INFECTIONS...BEST TO ADMIN... PARENTERALLY...6-12 G/DAY. ...MENINGITIS REQUIRES...300-400 MG/KG/DAY PARENTERALLY (IN EQUALLY DIVIDED PORTIONS...EVERY 4 HR) FOR CHILDREN, & 12 G OR MORE/DAY FOR ADULTS. DOSE VARIES WITH TYPE & SEVERITY OF INFECTION...RENAL FUNCTION &...AGE. FOR CHILDREN.../NOT/ ON BASIS OF BODY WT OR SURFACE AREA; BECAUSE DRUG...EXCRETED MAINLY BY KIDNEY ...RENAL FUNCTION TO GREAT EXTENT DETERMINES DOSE. VERY YOUNG BABIES...REQUIRE SMALL DOSES ...CHILDREN 3-4 YR.../DOSE/ ALMOST AS LARGE AS...ADULTS. Ampicillin /is/ indicated in the treatment of acute otitis media caused by susceptible organisms. /Included in US product labeling/ For more Therapeutic Uses (Complete) data for AMPICILLIN (18 total), please visit the HSDB record page. Drug Warnings IN 1 INSTANCE, FATAL PSEUDOMEMBRANOUS COLITIS OCCURRED FOLLOWING 5 DAYS OF ORAL AMPICILLIN THERAPY IN DOSAGE OF 2 G DAILY. VERY RARELY, AMPICILLIN HAS PRODUCED INTERSTITIAL NEPHRITIS; 1 CASE OF INTERSTITIAL NEPHRITIS REPORTEDLY PROGRESSED TO ACUTE RENAL FAILURE. ...CRYSTALLURIA HAS BEEN REPORTED... PERIODIC ASSESSMENT OF RENAL, HEPATIC & HEMATOPOIETIC FUNCTION SHOULD BE CONDUCTED DURING PROLONGED THERAPY, ESP IN PREMATURE, NEWBORN & OTHER INFANTS. ABSORPTION EFFICIENCY & RATE OF ELIMINATION OF AMPICILLIN...DECR IN PT WITH SHIGELLOSIS. POOR ABSORPTION...GENERALLY OBSERVED IN YOUNGER PATIENTS WITH MARKED DIARRHEA. ... DELAYED EXCRETION. MARKED RETENTION...IN PLASMA...NOTED IN PT WITH RENAL FAILURE. NATIONAL REGISTRY OF POSSIBLE DRUG INDUCED OCULAR SIDE EFFECTS ESTABLISHED IN 1975 BY FDA IN ORDER TO MAKE PHYSICIANS AWARE THAT SOME DRUGS SUCH AS AMPICILLIN MAY CAUSE SIDE EFFECTS TO EYE IS DISCUSSED. For more Drug Warnings (Complete) data for AMPICILLIN (16 total), please visit the HSDB record page. Pharmacodynamics Ampicillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Ampicillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Ampicillin results from the inhibition of cell wall synthesis and is mediated through Ampicillin binding to penicillin binding proteins (PBPs). Ampicillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. |
Solubility Data
| Solubility (In Vitro) |
0.1 M NaOH : ~25 mg/mL (~71.55 mM) H2O : ~4.9 mg/mL (~14.02 mM) |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8620 mL | 14.3102 mL | 28.6205 mL | |
| 5 mM | 0.5724 mL | 2.8620 mL | 5.7241 mL | |
| 10 mM | 0.2862 mL | 1.4310 mL | 2.8620 mL |