Ampicillin

Pharmaceuticals -> Antibiotics

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Antibiotics (Penicillins)

White, crystalline powder

White crystalline powder or as white, needle-like crystals

SOL IN WATER, DIMETHYL SULFOXIDE; DECOMP @ 199-202 °C; SPECIFIC ROTATION: +287.9 DEG @ 23 °C/D (WATER) /ANHYDROUS FORM/

CRYSTALS FROM WATER; SPARINGLY SOL IN WATER @ ROOM TEMPERATURE; DECOMP @ 202 °C; SPECIFIC ROTATION: +281 DEG @ 21 °C/D (WATER) /MONOHYDRATE/

1 Gm dissolves in about 90 ml of water, 20 ml of methanol, 250 ml of absolute ethanol, 13 ml of dimethylacetamide, and less than 10 ml of dimethylsulfoxide; practically insoluble in ether, ethyl acetate, petroleum ether, benzene, and chloroform.

In water, 10.1X10+3 mg/l at 21 °C

1.01E+004 mg/L (at 21 °C)

Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Antibacterial Agents; Penicillins

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Access group antibiotics

Active Ingredients (Ampicillin Anhydrous) -> FDA Greenbook

Pharmaceuticals -> Animal Drugs -> Approved in Taiwan

Pharmaceuticals -> UK Veterinary Medicines Directorate List

202 °C, with decomposition

208 °C

The stability of ampicillin sodium in soln is concn dependent and decreased as the concn of the drug increases. Ampicillin sodium appears to be especially susceptible to inactivation in soln containing dextrose, which appears to have a catalytic effect on hydrolysis of the drug.

... When stored @ room temperature (25 °C), ampicillin sodium soln containing 30 mg or less of ampicillin per ml in sterile water for injection, 0.9% sodium chloride injection, 1/6 M sodium lactate injection, or lactated Ringer's injection lose less than 10% of activity within 8 hr and soln containing 2 mg or less of ampicillin per ml in 5% dextrose, 5% dextrose and 0.45% sodium chloride, or 10% invert sugar lose less than 10% of activity within 4 hr. At concn of 10-20 mg/ml in 5% dextrose, ampicillin loses less than 10% of its activity within 2 hr @ room temperature.

When refrigerated @ 4 °C, ampicillin sodium soln containing 30 mg of ampicillin per ml are stable for 48 hr in sterile water for injection or 0.9% sodium chloride injection and soln containing 30 mg or less per ml are stable for 24 hr in lactated Ringer's or 8 hr in 1/6 M sodium lactate injection. Soln of the drug containing 20 mg or less of ampicillin per ml are stable @ 4 °C for 72 hr in sterile water for injection or 0.9% sodium chloride injection, 4 hr in 5% dextrose, or 3 hr in 10% invert sugar and soln containing 10 mg or less per ml are stable for 4 hr @ 4 °C in 5% dextrose and 0.45% sodium chloride.

Following reconstitution of the commercially available 10-g pharmacy bulk package of ampicillin sodium, soln containing 100 mg of ampicillin per ml should either be used or discarded within 2 hr if stored @ room temperature or within 4 hr if refrigerated.

For more Stability/Shelf Life (Complete) data for AMPICILLIN (6 total), please visit the HSDB record page.

This chemical does not meet GHS hazard criteria for 0.6% (1 of 167) of reports.

Danger

H315 (26.3%): Causes skin irritation [Warning Skin corrosion/irritation]

P233, P260, P261, P264, P264+P265, P271, P272, P273, P280, P284, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P333+P317, P337+P317, P342+P316, P362+P364, P391, P403, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 167 reports by companies from 12 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Status: Active Update: 20-04-2020 https://echa.europa.eu/registration-dossier/-/registered-dossier/11498

Ampicillin: Does not have an individual approval but may be used under an appropriate group standard

Oral Dosage Form New Animal Drugs. Specifications and conditions of use for dogs and cats. /Ampicillin capsules/

Oral Dosage Form New Animal Drugs. Specifications and conditions of use for dogs. /Ampicillin trihydrate tablets/

Oral Dosage Form New Animal Drugs. Specifications and conditions of use for dogs and cats. /Ampicillin trihydrate capsules/

Oral Dosage Form New Animal Drugs. Specifications and conditions of use for dogs and cats. /Ampicillin trihydrate for oral suspension/

For more FDA Requirements (Complete) data for AMPICILLIN (11 total), please visit the HSDB record page.

Ampicillin capsules and powder for oral suspension should be stored in tight containers @ 15-30 °C. Following reconstitution, oral suspensions of either anhydrous ampicillin or ampicillin trihydrate should preferable be refrigerated @ 2-8 °C but are stable for 7 days @ room temperature or 14 days @ 2-8 °C.

Following reconstitution with sterile or bacteriostatic water for injection, ampicillin sodium solutions for IM or direct IV injection should be used within 1 hr after reconstitution and should not be frozen.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

...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.

The rate of serum aminotransferase and alkaline phosphatase elevations during ampicillin therapy is not well defined. High dose, intravenous ampicillin has been associated with ALT elevations in 9% to 11% of patients, but a similar rate is often found in comparator arms and the elevations are generally transient and asymptomatic. Rare instances of idiosyncratic liver injury have been reported in persons receiving the aminopenicillins, but they are rarely listed in large case series or prospective databases on drug-induced liver injury. The incidence of clinically apparent liver injury is far lower with ampicillin than occurs with amoxicillin, occurring probably in less than 1 in 200,000 exposed persons. Cases are characterized by a short latency period of a few days to as long as six 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.

Skin Sensitizer - An agent that can induce an allergic reaction in the skin.

Serious Adverse Drug Reactions

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. /Ampicillin trihydrate/ [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=7177-48-2]

AGRANULOCYTOSIS WITH PERIPHERAL MONOCYTOSIS & BONE-MARROW HISTIOCYTOSIS HAS BEEN REPORTED FOLLOWING TREATMENT WITH AMPICILLIN.

Ampicillin has comparatively few adverse properties, permitting it to be used preferentially over other agents such as chloramphenicol or tetracyclines when a broad-spectrum antibacterial drug is desired. It has been used as treatment for urinary, respiratory, and GI infections and bacterial otitis. Since ampicillin is excreted in bile, it can be used to treat biliary tract infections. Superinfections caused by Enterobacter, Pseudomonas, or Candida have occurred during oral ampicillin therapy, necessitating a reduced dose or substitution of another antibacterial drug.

Ampicillin reportedly induces environmental or occupational asthma possibly by IgE mediation /from table/

GI side effects of ampicillin include diarrhea, nausea/vomiting, epigastric/abdominal pain, and stomatitis/glossitis /from table/

For more Human Toxicity Excerpts (Complete) data for AMPICILLIN (59 total), please visit the HSDB record page.

Ampicillin

Group 3: Not classifiable as to its carcinogenicity to humans

Volume 50: (1990) Pharmaceutical Drugs

1990

1989

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

ampicillin

DILI Positive

Oral

DOI:10.1016/j.drudis.2019.09.022

DEATH FROM RESP FAILURE WITH OR WITHOUT CONVULSIONS OCCURRED 6-18 HR AFTER SINGLE ORAL DOSES. ACUTE GASTROENTERITIS & CARDIOVASCULAR SHOCK WERE ASSOCIATED PHENOMENA. ...PATTERN...ALSO TRUE FOR GUINEA PIGS EXCEPT THAT LATE (1-2 WK) & GRADUALLY DEVELOPING TOXEMIA KILLED ALL SURVIVORS OF ACUTE RESPONSE. /PENICILLINS/

IN HAMSTERS...SOMEWHAT MORE TOXIC BY ORAL THAN BY SC ROUTE WHEN OBSERVED FOR 14 DAYS AFTER SINGLE DOSES. TOLERANCE DEVELOPED TO MULTIPLE DOSING. PERHAPS SENSITIVITY OF GUINEA PIGS IS RELATED TO EFFECTS ON INTESTINAL MICROFLORA. SC LD50 IN NEWBORN (LESS THAN 72 HR) RATS WAS 7-FOLD LOWER THAN LD50 IN ADULTS. /PENICILLINS/

Ampicillin may have an adverse effect on rabbits when administered orally. Rabbits that consumed 18.8 mg ampicillin/100 ml drinking water developed diarrhea and died within a month. Severe enteritis and renal tubular damage was thought to be related to an antibiotic-induced disturbance of intestinal bacterial equilibrium. The oral dose of ampicillin is approximately 12 mg/kg 4 times daily.

Ampicillin has been used in a variety of domestic animals at doses ranging from 2 to 50 mg/kg. Blood concentrations are dose dependent and the maintenance dose must be administered at 4- to 6-hour intervals. Although ampicillin disappears from the blood quite rapidly, it appears that tissue concentrations may be greater than blood concentrations for a significant therapeutic effect; eg, /it was/ reported that uterine tissue concentrations in the mare were 10-50% higher than serum. They recommended an IV dose of 11-16 mg ampicillin/kg at 4- to 8-hour intervals. Ampicillin has been used to treat bacterial infections in cattle. A dose of 4.5-11 mg/kg was administered parenterally once daily for 3 days. Clinical improvement was noted in 86% of the cases and adverse effect were noted in experimental tests.

For more Non-Human Toxicity Excerpts (Complete) data for AMPICILLIN (17 total), please visit the HSDB record page.

Evaluation: There is inadequate evidence for the carcinogenicity of ampicillin in humans. There is limited evidence for the carcinogenicity of ampicillin in experimental animals. Overall evaluation: Ampicillin is not classifiable as to its carcinogenicity to humans (Group 3).

Toxicology and carcinogenesis studies of ampicillin trihydrate (97-99% pure) were conducted by administering the chemical in corn oil by gavage to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex, 5 days/wk for 103 wk. Male and female rats received doses of 0, 750, or 1,500 mg/kg, and male and female mice received doses of 0, 1,500 or 3,000 mg/kg. ... Under the conditions of these 2 yr gavage studies, there was equivocal evidence of carcinogenicity of ampicillin trihydrate for male F344/N rats as shown by increased incidences of pheochromocytomas of the adrenal medulla and marginally increased incidences of mononuclear cell leukemia. There was no evidence of carcinogenicity for female F344/N rats receiving 750 or 1,500 mg/kg or for male or female B6C3F1 mice receiving 1,500 or 3,000 mg/kg per day. Noneoplastic lesions of the forestomach were seen in male rats and male and female mice. /Ampicillin trihydrate/

Oral Dosage Form New Animal Drugs. Specifications and conditions of use for dogs and cats. /Ampicillin capsules/

Oral Dosage Form New Animal Drugs. Specifications and conditions of use for dogs. /Ampicillin trihydrate tablets/

Oral Dosage Form New Animal Drugs. Specifications and conditions of use for dogs and cats. /Ampicillin trihydrate capsules/

Oral Dosage Form New Animal Drugs. Specifications and conditions of use for dogs and cats. /Ampicillin trihydrate for oral suspension/

For more FDA Requirements (Complete) data for AMPICILLIN (11 total), please visit the HSDB record page.

J - Antiinfectives for systemic use

S - Sensory organs

QJ - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

QS - Sensory organs

J01CA01

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 <i>in vitro</i> 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.

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/

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 ... .

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 ... .

7C782967RD

AMPICILLIN

Established Pharmacologic Class [EPC] - Penicillin-class Antibacterial

Chemical Structure [CS] - Penicillins

Ampicillin is a Penicillin-class Antibacterial.

AMPICILLIN

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.

Ampicillin is a broad-spectrum antibiotic. The clinical indications for ampicillin cover a variety of infections, including those of the respiratory and urinary tracts, gonorrhoea, meningitis, septicaemia and enteric infections.

MEDICATION

Use (kg; approx.) in Germany (2009): >10000

Impurities of ampicillin that occur during preparation of the product are D-(-)-alpha-phenylglycine and 6-aminopenicillanic acid. It has been reported that sodium ampicillin in aqueous solution undergoes a reaction to form oligomeric products.

(1978) 7.51X10+7 GRAMS (INCL SALTS)

(1979) 1.89X10+7 GRAMS (INCL SALTS)

(1977) 3.83X10+7 GRAMS (PRINCPL CUSTMS DISTS)

(1979) 2.25X10+7 GRAMS (PRINCPL CUSTMS DISTS)

(1977) 5.30X10+8 GRAMS

(1979) 4.53X10+8 GRAMS

ACYLATION OF 6-AMINOPENICILLANIC ACID WITH D-(-)-GLYCINE

DOYLE ET AL, US PATENT 2,985,648 (1961); EIDEM, BRITISH PATENT 902,703 (1962 TO BEECHAM); DOYLE ET AL, J CHEM SOC 1962, 1440; KAUFMANN, BAUER, US PATENT 3,079,307 (1963 TO BAYER); JOHNSON, WOLFE, & JOHNSON, HARDCASTLE, US PATENTS 3,140,282 & 3,157,640 (BOTH 1964 TO BRISTOL-MYERS)...

...GRANT, ALBURN, US PATENT 3,144,445 (1964 TO AM HOME PRODUCTS); DANE, DOCKNER, BER 98, 789 (1965). ... DL-FORM.../OF SODIUM SALT/ BRITISH PATENT 958,824 (1964 TO PFIZER).

Ampicillin is produced by the acylation of 6-aminopenicillanic acid with D-(-)-alpha-phenylglycine by either microbiological or chemical synthesis.

USP anhydrous ampicillin contains 900-1050 ug/mg ampicillin (calculated as the anhydrous base). Ampicillin is available in 125-, 200-, 250-, and 500-mg tablets that contain 90-120% labelled active ingredient, in 125-, 250-, and 500-mg capsules containing 90-120% labelled active ingredient, and as oral suspensions of 100, 125, and 250 mg/5 ml containing 90-120% of the labelled active ingredient and probenecid.

Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients

Veterinary Drug -> ANTIMICROBIAL_AGENT; Veterinary Drug -> -> JECFA Functional Classes

Pharmaceuticals -> Animal Drugs -> Approved in Taiwan

HAS BEEN USED CLINICALLY TO IMPROVE FERTILITY IN KENNEL BY TREATING STUD DOG TO ELIMINATE BACTERIAL CONTAMINATION OF SEMEN. ... IN US... NOT RECOMMENDED FOR USE IN FOOD PRODUCING ANIMALS EXCEPT SWINE. TOLERANCE OF 0.01 PPM FOR...RESIDUES IN UNCOOKED EDIBLE TISSUES OF SWINE IS PERMITTED...