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Ampicillin

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 b-lactamases, including penicillinases, and cephalosporinases and extended spectrum b-lactamases. The compound, (6[D( - )-a-aminophenylacetamido] penicillanic acid), was synthetised in 1061 [1] and its preliminary pharmacology was reported[2-3].

Therapeutic use

For treatment of infection (Respiratory, GI, UTI and meningitis) due to E. coli, P. mirabilis, enterococci, Shigella, S. typhosa and other Salmonellae, nonpenicillinase-producing N. gononhoeae, H. influenzae, staphylococci, streptococci.

 

Dosage and Administration

 

Toxicology

Ampicillin is relatively non-toxic. Its most common side effects include rash, diarrhea, nausea and vomiting. In very rare cases it causes severe side effects such as anaphylaxis and Clostridium difficile diarrhea.

Organism Test Type Route Reported Dose (Normalized Dose) Effect Source
cat LDLo intravenous > 100mg/kg (100mg/kg)   British Medical Journal. Vol. 2, Pg. 197, 1961.
guinea pig LD50 unreported 7500ug/kg (7.5mg/kg)   Gigiena i Sanitariya. For English translation, see HYSAAV. Vol. 42(9), Pg. 10, 1977.
man TDLo oral 400mg/kg/4W-I (400mg/kg) BLOOD: AGRANULOCYTOSIS

BLOOD: OTHER CHANGES
Annals of Internal Medicine. Vol. 69, Pg. 91, 1968.
 
mouse LD50 intracrebral 380mg/kg (380mg/kg) BEHAVIORAL: EXCITEMENT

MUSCULOSKELETAL: CHANGES IN TEETH AND SUPPORTING STRUCTURES

BEHAVIORAL: "HALLUCINATIONS, DISTORTED PERCEPTIONS"
Chemotherapy Vol. 26, Pg. 196, 1980.
mouse LD50 intraperitoneal 3250mg/kg (3250mg/kg) BRAIN AND COVERINGS: RECORDINGS FROM SPECIFIC AREAS OF CNS

BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)
Eksperimental'naya i Klinicheskaya Farmakoterapiya. Vol. 9, Pg. 83, 1980.
mouse LD50 intravenous 4600mg/kg (4600mg/kg)   Yakugaku Zasshi. Journal of Pharmacy. Vol. 97, Pg. 987, 1977.
mouse LD50 oral > 5gm/kg (5000mg/kg)   Drugs in Japan Vol. 6, Pg. 57, 1982.
mouse LD50 parenteral > 3gm/kg (3000mg/kg)   Drugs in Japan Vol. -, Pg. 114, 1995.
mouse LD50 unreported 28gm/kg (28000mg/kg)   Gigiena i Sanitariya. For English translation, see HYSAAV. Vol. 42(9), Pg. 10, 1977.
mouse LDLo subcutaneous > 5gm/kg (5000mg/kg)   British Medical Journal. Vol. 2, Pg. 197, 1961.
rat LD50 intraperitoneal 4500mg/kg (4500mg/kg)   Toxicology and Applied Pharmacology. Vol. 18, Pg. 185, 1971.
rat LD50 intravenous 6200mg/kg (6200mg/kg)   Drugs in Japan Vol. -, Pg. 88, 1990.
rat LD50 parenteral > 3gm/kg (3000mg/kg)   Drugs in Japan Vol. -, Pg. 114, 1995.
rat LD50 unreported 10gm/kg (10000mg/kg)   Gigiena i Sanitariya. For English translation, see HYSAAV. Vol. 42(9), Pg. 10, 1977.
rat LDLo oral > 5gm/kg (5000mg/kg)   British Medical Journal. Vol. 2, Pg. 197, 1961.
rat LDLo subcutaneous > 5gm/kg (5000mg/kg)   British Medical Journal. Vol. 2, Pg. 197, 1961.
women TDLo oral 160mg/kg/4D-I (160mg/kg) BLOOD: THROMBOCYTOPENIA

BLOOD: AGRANULOCYTOSIS
Annals of Internal Medicine. Vol. 99, Pg. 573, 1983.

Acute toxicity

The acute toxicity was determined in male albino mice (Edwards strain-18 to 22 g) after intravenous, subcutaneous and oral administration, and in Sprague-Dawley rats (150 to 200 g) after subcutaneous and oral administration.

Ampicillin is non-toxic to mice and rats when administered either orally or subcutaneously in doses of 5 g/kg. Intravenous dosage of 2 g/kg in mice did not give lethal effects, although muscle tremors, slowed respiration and mild clonic convulsions have sometimes occurred. The amount which can be administered intravenously was limited by solubility, and the maximum dose was 2.5 g/kg. At this dose level 3 out of 10 mice died.

Prolonged administration

Rats. Doses of 500 and 100 mg/kg were administered orally by stomach tube to groups of 12 male rats, 5 days per week for a period of 12 weeks. The dose was administered as a freshly prepared aqueous solution in a voludie equivalent to 0.5 ml/100 g body weight. The control group received an equivalent volume of tap water. Daily food intake and the weight of each rat was recorded. Weekly records of the red and white blood cell counts and qualitative tests for sugar and protein in the urine were performed. Haemoglobin determinations and spectroscopic examination of the blood were made on the first, sixth and twelfth week of the test. At the end of 12 weeks all the rats were killed and the weights of the livers, spleens; kidneys, testes and adrenals were recorded. Specimens of liver, spleen, kidney, lung, thyroid, heart, duodenum, stomach, pancreas, adrenal, testis and bone marrow were removed from 6 animals in each group for histological examination.

Dogs. Ampicillin (250 mg/kg) was administered orally twice daily for a period of 4 weeks to 2 dogs. The following biochemical and haematological estimations were made at weekly intervals: haemoglobin (%), packed cell volume, total white cell count, blood urea, serum alkaline phosphatase, zinc sulphate turbidity and serum globulin and albumin. A differential blood cell count was carried out at the end of the first and final week of the test.

No toxic symptoms were noted in rats treated with ampicillin. Similarly there were no observable toxic symptoms in dogs apart from a slight loosening of the stools during the early days of the test. Post-mortem examination did not reveal any abnormalities in either species, and the histology of the organs examined was normal.

Local irritation

5 %/ and 1 %, solutions were injected intramuscularly and intradermally into guinea-pigs (3 per group). The solutions were administered in a volume of 0.1 ml. intramuscularly into the hind legs, and 0.05 ml. intradermally in a shaved area on the back. After 24 hr the area of the injection was examined and the skin and subcutaneous tissues were removed for histological examination.

The effect of ampicillin on the eye was examined in a group of 3 rabbits. A 25% solution in normal saline was dropped into a pocket formed by pulling out the lower left eyelid. The solution was held over the eye for 1 min. Saline was similarly applied to the right eye. The
eyes were examined at 1, 2, 4, 8 and 24 hr afterwards for signs of irritation.

No macroscopical signs of damage were observed apart from a slight area of erythema at the site of injection. Microscopical changes in the skin and muscle were minimal and difficult to find. They consisted only of very sparse inflammatory cell infiltration and slight accompanying interstitial fluid accumulation.

Safety pharmacology

Blood pressure and respiratory effects. The carotid blood pressures of 5 cats anaesthetized with a 40% urethane/1%, chloralose mixture (5 ml/kg intravenously) were recorded manometrically on a smoked drum. Respiration was recorded by a lever connected to a thread which was sewn to the skin over the xiphisternum. Ampicillin in physiological saline was administered intravenously through the femoral vein at intervals of 5 min.

Doses up to 80 mg/kg, administered intravenously to cats, had no effect on blood pressure or respiration. Neither had they any effect on the blood pressure response to an injection of adrenaline, acetylcholine or histamine.

 

Pharmacokinetic

Protein binding

Ampicillin is considerably less bound to serum proteins than phenoxymethyl penicillin (Table 1).

Table 1. protein binding of ampicillin and pjenoxymethyl penicillin to bovine, horse and human serum.

  Mean % serum bound
Antibiotic bovine horse human
ampicillin 17.15 7.9 17.0
phenoxymethyl penicillin 51.37 39.37 68.7

 

Bioavailability 40%
Protein binding 15 to 25%
Metabolism 12 to 50%
Half-life 1 hr
Cmax (mg/ml)  
tmax (hrs)  
Distribution volume Vd  
Clearance  
Excretion 75 to 85% renal

Absorption

Rabbits. The blood levels obtained after oral and intramuscular administration of phenoxymethyl penicillin and ampicillin are given in Table 2. After intramuscular dosing the peak level of phenoxymethyl penicillin at 1 hr is higher than ampicillin, but at subsequent periods the concentrations of both antibiotics are similar. On the other hand, after oral administration the concentrations of ampicillin are considerably greater than phenoxymethyl penicillin.

Table 2. Mean blood concentration following oral and intramuscular administration of 100mg/kg of ampicillin and phenoxymethyl penicillin to groups of 5 rabbits.

  Concentration mg/ml
Time (hrs) ampicillin phenoxymetyl penicillin administration route
1 3.0 4.7 Intramuscular
2 2.91 2.42  
3 0.73 0.65  
4 0.13 0.22  
1 2.16 0.67 Oral
2 0.92 0.5  
3 0.27 0.03  
4 0.06 0  

Dogs. The mean serum. concentrations after 20 mg/kg of ampicillin and phenoxymethyl penicillin given orally and of 5 mg/kg ampicillin and benzylpenicillin given intramuscularly are shown in Table 3. Following the oral administration of phenoxymethyl penicillin, the highest blood concentration recorded occurred 30 min after administration, whereas with ampicillin the highest concentration occurred 1 hr afterwards. Throughout the 5 hr period of the test, when blood samples were taken regularly, the concentration of ampicillin was always considerably higher than phenoxymethyl penicillin. After intramuscular administration the peak serum concentrations of ampicillin and benzylpenicillin occur at 30 min. Throughout the period of the test the concentrations of ampicillin were greater than benzylpenicillin.

Table 3. Mean serum concentration in groups of 5 dogs after oral (20mg/kg) and intramuscular (5mg/kg) administration of of ampicillin and phenoxymethyl penicillin.

  Concentration mg/ml
Time (hrs) ampicillin phenoxymetyl penicillin ampicillin phenoxymetyl penicillin
  Oral Intramuscular
0.5 4.87 2.58 4.6 2.1
1 7.23 1.48 3.3 0.76
1.5 3.67 0.59 1.55 0.48
2 3.51 _ 0.95 0.26
2.5 2.15 0.15 _ _
3 0.96 0.1 0.32 _
3.5 0.4 0.08 0.13 0.06
4 0.32 0.07 0.09 0.03
4.5 0.22 0.07 0.09 0.01
5 0.19 0.04    
5.5 0.11 0.04    
24 0 0    

Distribution

Cerebrospinal fluid. Ampicillin penetrates into the cerebrospinal fluid with difficulty. The concentrations in the cerebrospinal fluid after doses of 500 mg/kg intramuscularly at 1, 2, 4 and 6 hrs following administration are respectively 1.4, 0.12, 0.05 and 0.13 mg/ml., whereas the corresponding levels in the serum are 54.0, 14.25, 4.2 and 5.8 mg/ml.

Tissue distribution. The amounts of ampicillin recovered from the various tissues after oral and intramuscular administration are shown in Tables 4 and 5. The amounts are expressed in mg/g wet weight (column a) and as the ratio of concentration in the tissues to the concentration in the serum (column b). The values represent the mean of 10 rats. The amount of the antibiotic recovered expressed
as a percentage of the dose administered is shown in the tables. After oral administration the concentration of ampicillin fell off more rapidly in the serum than any other tissue, with the exception of the spleen. The high concentrations in the livers and kidneys were probably accounted for by the presence of bile and urine in these organs. The passage of the antibiotic along the alimentary canal is well illustrated. The antibiotic passed very rapidly from the stomach to the small intestine. There were only trace amounts found in the colon for the first 2 hr of the test, but at 4 hr large quantities were recovered in the colon and faeces. Throughout the period of the test the total quantity recovered decreased until at 12 and 24 hr only 9.6% and 4.3% of the doses administered were recoverable; the majority of these quantities were in the urine, 6.6% and 3.7% respectively. After oral administration 43 to 65% can be recovered in the first 4 hr.

After intramuscular administration there is a rapid increase of serum level during the first half-hour following administration; however, this is followed by a very rapid decrease in serum levels. Within 4 hr serum levels have been reduced from 64.4 mg/ml. to 0.18 3 mg/ml. Practically the whole of the amount injected is recovered in the urine within 1 to 2 hr after administration. The concentrations occurring in the liver and the kidneys are also initially very high, and they decline very rapidly but not quite at the same speed as the serum levels. The concentrations in the spleen and lung during the first hour never reach the concentration found in the serum, but the decline in the concentrations in these two organs is much less than in the serum, so that at the end of 4 hr the concentrations are higher than the serum. The amount found in the small intestine and the large intestine resulting probably from biliary excretion does not exceed 6.5% of the dose administered. After intramuscular injection 73 to 117% can be recovered in the first 4 hrs.

Table 4. Distribution of ampicillin in rats after oral administration.

  0.5 hrs 1 hr 2 hrs 4 hrs 12 hrs 24 hrs
Organ a b a b a b a b a b a b
Liver 15.82 3.58 18.0 9.18 8.16 9.27 2.17 27.13 0.08 6.4 0 _
Spleen 2.22 0.5 0.39 0.2 0.33 0.38 0.12 1.5 0.03 2.64 0.05 _
Kidneys 13.22 2.99 9.86 5.03 6.31 7.17 1.04 13.0 0.06 5.0 0 _
Lungs 6.17 1.4 1.72 0.88 1.29 1.47 1.08 13.5 0.03 1.8 0.08 _
Stomach 706.0 159.7 372.4 190.0 198.0 225.0 5.65 70.63 8.75 700.0 0.09 _
Small intestine 1230.0 278.3 1260.0 642.9 666.0 756.8 37.66 470.7 1.15 92.0 0.13 _
Caecum, colon 2.41 0.55 0.35 0.18 531.9 604.5 1482.0 18525.0 73.5 5880.0 2.77 _
Faeces 0 0 0 0 0.104 0.12 660.8 8260.0 26.18 2094.0 77.5 _
Carcass 3.57 0.81 0.71 0.36 1.95 2.22 0.68 8.5 0.125 10.0 0 _
Serum 4.42 1.0 1.96 1.0 0.88 1.0 0.88 1.0 0.012 1.0 0 _
% urine excreted 0.2 0.87 3.11 4.34 6.63 3.7
% dose recovered 64.8 57.9 45.03 42.65 9.61 4.31

Seven groups of 10 rats were given orally 100mg/kg of ampicillin. One group was killed at the end of each time period. The mean concentration of ampicillin is expressed in mg/ml wet weight of tissue (column a) and the concentration ratio between the tissues mg/g wet weight to serum mg/ml is shown in column b. The urinary excretion is expressed as % of the dose administered.

Table 5. Distribution of ampicillin given intramuscularly in rats.

  0.5 hrs 1 hr 2 hrs 4 hrs
Organ a b a b a b a b
Liver 175.0 2.7 70.48 4.6 5.76 6.1 0.98 5.4
Spleen 8.3 0.13 3.4 0.22 0.76 0.8 0.24 1.3
Kidneys 288.0 4.4 146.2 9.6 6.56 6.9 0.75 4.2
Lungs 28.6 0.44 6.7 0.44 1.18 1.3 0.52 2.9
Small intestine 77.4 1.2 11.7 7.3 70.8 75.3 15.56 86.4
Large intestine 6.74 0.1 5.24 0.34 20.1 21.4 105.8 587.7
Site of injection 132.0 2.01 31.4 2.1 3.86 41.1 1.86 10.3
Carcass 17.9 0.28 4.54 0.3 0.78 0.8 0.85 4.7
Urine 2548.0 3.9 4105.0 268.7 2626.0 2793.6 1452.0 8066.6
Serum 64.4 1.0 15.28 1.0 0.94 1.0 0.18 1.0
Faeces         13.0 13.8 23.32 129.5
% urine excreted 52.0 84.4 112.0 95.5
% dose recovered 73.2 99.4 116.9 99.9

Five groups of 10 rats were injected intramuscularly with 100mg/kg ampicillin. One group was killed at the end of each time period. The mean concentration of ampicillin is expressed in mg/ml wet weight of tissue (column a) and the concentration ratio between the tissues mg/g wet weight to serum mg/ml is shown in column b. The urinary excretion is expressed as % of the dose administered.

Excretion

Ampicillin is eliminated unchanged from the body in high concentrations in the bile and urine. Almost all of the antibiotic can be accounted for in the urine and intestinal contents 2 hr after intramuscular administration but not after oral administration.

Rat. The percentage of dose excreted in the bile and urine and that remaining in the gut after the 25 hrs period of experimentation are shown in Table 6. Maximum biliary excretion occurred in the 2 to 4 hr period after dosing and there was no excretion in the bile after 23 hrs. No urine samples were obtained during the first 2-hr period, and maximum urinary excretion occurred within 4 hrs of dosing. Over the 25 hrs period approximately twice as much ampicillin was excreted in the urine as compared with that excreted in the bile. In only one rat there was any appreciable quantity of ampicillin remaining in the small intestine after 25 hr. Similarly, the colon, caecum, rectum and faeces of only one rat contained a significant quantity of ampicillin after 25 hrs. Approximately 7% of the dose could be accounted for in the bile, urine and faeces.

Table 6. Absorption and excretion of ampicillin in the conscious rat after intraduodenal dosing at 100mg/kg.

    Bile

% of dose excreted (hrs)

Urine

% of dose excreted (hrs)

Blood levels

Concentration mg/ml (hr)

% dose remaining in gut after 25 hrs
Rat nr. Dose

(mg)

1-2 2-4 4-6 6-23 23-25 1-2 2-4 4-6 6-23 23-25 1 3 5 24 small intestine Colon, caecum, rectum, faeces
1 32 0.21 0.83 0.19 0.25 0 nd 0.53 0.04 0.63 nd 0.52 0.36 0.21 0 0.01 0.09
2 43 0.66 0.78 0.28 0.70 0 nd nd 2.39 2.06 0.04 0.94 0.52 0.46 0 0 2.64
3 29 0.72 0.38 0.10 0.21 0 nd 1.32 0.35 0.84 0 1.35 0.56 0.28 0.11 2.71 0
4 30 0.16 0.71 0.18 0.06 0 nd 0.97 2.49 0.26 0 3.00 0.42 0.17 0 0 0
5 41 0.98 1.80 1.37 0.16 0 nd 3.76 nd 2.95 0.01 0.60 0.88 0.76 0 0.06 0
mean   0.55 0.90 0.42 .28 0 nd 1.65 1.32 1.35 0.01 1.28 0.55 0.38 0.02 0.56 0.55

Table 7 shows the mean blood, urine and bile concentrations of phenoxymethyl penicillin and ampicillin at 2-hr intervals following the administration of 100 mg/kg orally of each antibiotic in conscious rat. The mean ratios show that there is little difference between the two antibiotics regarding the blood/bile concentration, the bile concentration being approximately 300 times that found in the blood. However, the concentration of ampicillin in the urine is twice that of phenoxymethyl penicillin, and the mean blood to urine concentration ratios of each antibiotic are 800 for ampicillin and 400 for phenoxymethyl penicillin.

Table 7. Mean concentrations in blood, urine and bile, % of dose excreted in urine and bile, and ratio of urine and bile to blood concentrations after oral administration of 100mg/kg of ampicillin and phenoxymethyl penicillin to groups of 10 conscious rats.

  Blood concentration (mg/ml) Urine concentration (mg/ml) Bile concentration (mg/ml) % of dose excreted in urine % of dose excreted in bile ratio of urine to blood concentration ratio of bile to blood concentration
Time (hrs) AMP PMP AMP PMP AMP PMP AMP PMP AMP PMP AMP PMP AMP PMP
0-2 0.25 1.42 171.4 546.5 65.9 441.0 0.69 3.55 0.27 3.05 690 385 265 311
2-4 0.41 1.25 234.8 384.6 95.3 503.6 1.46 3.90 0.65 4.19 569 303 231 397
4-6 0.19 0.41 235.2 225.8 83.7 96.6 1.08 0.66 0.41 0.55 1.238 551 441 236

AMP = ampicillin, PMP = phenoxymethyl penicillin

Metabolism

Urinary excretion-the hen. In hens treated with ampicillin only, almost all of the antibiotic administered is excreted in the urine during the 6-hrs period following intramuscular administration into the left leg. Four to five times more is excreted by the left kidney than by the right kidney. After probenecid which blocks renal tubular filtration the mean total amount excreted by the left kidney is reduced to about 1.6 times that excreted by the right kidney; moreover, following probenecid approximately 66% of the injected dose only can be accounted for
during the period of test (see Table 8).

Table 8. The mean urinary excretion from the left and right kidneys of 4 hens each of which received 100 mg ampicillin and 100 mg ampicillin + 100 mg probenecid. Ampicillin was administered into the left leg muscles and probenecid into a wing vein.

    % of dose excreted
Treatment Time (hrs) left right
ampicillin 0-1 36.78 6.05
  1-2 19.10 4.49
  2-3 9.07 1.19
  3-4 7.34 1.40
  4-5 3.85 1.56
  5-6 1.64 1.99
  total 0-6 77.78 16.68
ampicillin with probenecid 0-1 18.56 12.75
  1-2 10.07 6.85
  2-3 5.51 1.99
  3-4 3.52 1.41
  4-5 1.93 1.87
  5-6 1.16 0.85
  total 0-6 40.75 25.72

 

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.

Antibacterial activity

 

In vivo efficacy

Studies with infected animals show that it is as effective as the existing oral penicillins against Staphylococcus pyogenes Smith (penicillin sensitive), Streptococcus pyogenes Group A and Diplococcus pneumoniae. It is ineffective against penicillin-resistant Staphylococci. When tested in mice infected with the gram-negative organisms, Salmonella typhimurium and Klebsiella pneumoniae, it was considerably more active than tetracycline and chloramphenicol.

Ampicillin is effective against a number of experimental infections produced by gram-negative and gram-positive organisms in mice (Table 9). Against the penicillin-sensitive staphylococci (Staphylococcus aureus Smith) ampicillin, benzylpenicillin and phenethicillin, given subcutaneously, are the most active antibiotics followed by phenoxymethyl penicillin and tetracycline; chloramphenicol is inactive.

Table 9. Activity of ampicillin, phenoxymethyl penicillin, pheneticillin, benzylpenicillin, tetracycline and chloramphenicol against Gram-positive and Gram.negative infections.

Expressed in terms of the dose of antibiotic calculated to protect 50% of a group of infected mice (CD50 mg/kg); n=number of observations

    In vitro MIC

(mg/ml)

Oral

Subcutaneous

Organism Antibiotic Mean CD50 mg/kg n Mean CD50 mg/kg n
Staphylococcus aureus Smith Ampicillin 0.1 0.3 4 0.3 4
  Phenoxymethyl penicillin 0.02 0.3 3 0.5 1
  benzylpenicillin 0.02 5.8 1 0.3 3
  phenethicillin 0.05 0.3 2 0.1 1
  tetracycline 0.1 5.2 1 6.0 1
  chloramphenicol 50 inactive 100 2 inactive 100 2
Staphylococcus aureus 52-75 Ampicillin >200 Inactive   Inactive  
  Phenoxymethyl penicillin >200 Inactive   Inactive  
  benzylpenicillin >200 Inactive   Inactive  
  phenethicillin >200 Inactive   Inactive  
  tetracycline >200 Inactive   Inactive  
  chloramphenicol >200 Inactive   Inactive  
Streptococcus pyogenes Group A Ampicillin 0.1 0.1 1 0.025  
  Phenoxymethyl penicillin 0.05 0.1 1 0.1 1
  benzylpenicillin 0.05 _   _  
  phenethicillin 0.2 0.5 1 0.1 1
  tetracycline 0.2 0.5 1 05 1
  chloramphenicol 2.0 3.2 1 3.2 1
Diplococcus pneumoniae Ampicillin 0.05 0.25 2 0.5 2
  Phenoxymethyl penicillin 0.05 0.6 2 0.9 2
  benzylpenicillin 0.02 _ 2 0.6 2
  phenethicillin 0.05 0.4 1 0.2 1
  tetracycline 0.2 13.0 1 5.0 2
  chloramphenicol 2.0 >100 1 Inactive 100 1
Klebsiella pneumoniae Ampicillin 0.5 11.6 9 35.4 8
  Phenoxymethyl penicillin 50.0 inactive 400 4 inactive 400 4
  benzylpenicillin 10.0 _   Inactive 400 3
  phenethicillin 500 inactive 400 2 inactive 400 2
  tetracycline 0.5 inactive 400   61.0 14
  chloramphenicol 1.0 165.0   280.0 2
Salmonella typhimurium Ampicillin 1.0 18.0 10 12.8 10
  Phenoxymethyl penicillin 200 inactive 400 4 inactive 400 4
  benzylpenicillin 10.0 inactive 400 3 82.0 3
  phenethicillin >100 inactive 400 2 inactive 400 2
  tetracycline 2.0 62.4 5 59.2 16
  chloramphenicol 5.0 310 1 250 3

When given by the oral route ampicillin, phenoxymethyl penicillin and phenethicillin are equally active, but the activity of benzylpenicillin is reduced to that of tetracycline; chloramphenicol again is inactive. None of the antibiotics is active against staphylococci resistant to benzylpenicillin. Against streptococci, ampicillin, phenoxymethyl penicillin, phenethicillin and tetracycline are all very active when given orally or subcutaneously, although mpicillin is the most active when given subcutaneously. Again, chloramphenicol is the least active.

Against pneumococci, ampicillin is the most active, followed by phenoxymethyl penicillin, phenethicillin and benzylpenicillin. Tetracycline is less active and chloramphenicol is only slightly active.

In the animals infected with gram-negative organisms, benzylpenicillin, phenethicillin and phenoxymethyl penicillin are inactive, while ampicillin is considerably more active than tetracycline, which in turn is more active than chloramphenicol, both orally and subcutaneously.

Other pharmacological effects


Medicinal Chemistry

CAS number:  69-53-4 EINECS: 200-709-7

Molecular Formula:  C16H19N3O4S

Average mass: 349.404785 Da

Monoisotopic mass:  349.109619 Da

Systematic 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

SMILES: CC1([C@@H](N2[C@H](S1)[C@@H](C2=O)NC(=O)[C@@H](C3=CC=CC=C3)N)C(=O)O)C

Std. 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)/t9-,10-,11+,14-/m1/s1

ACD/LogP: 1.350.32 # of Rule of 5 Violations: 0
ACD/LogD (pH 5.5): -1.18 ACD/LogD (pH 7.4): -1.97
ACD/BCF (pH 5.5): 1.00 ACD/BCF (pH 7.4): 1.00
ACD/KOC (pH 5.5): 1.00 ACD/KOC (pH 7.4): 1.00
#H bond acceptors: 7 #H bond donors: 4
#Freely Rotating Bonds: 5 Polar Surface Area: 138.03 2
Index of Refraction: 1.675 Molar Refractivity: 89.90.4 cm3
Molar Volume: 239.35.0 cm3 Polarizability: 35.70.5 10-24cm3
Surface Tension: 74.35.0 dyne/cm Density: 1.50.1 g/cm3
Flash Point: 367.431.5 C Enthalpy of Vaporization: 105.43.0 kJ/mol
Boiling Point: 683.955.0 C at 760 mmHg Vapour Pressure: 0.02.2 mmHg at 25C

Major Impurities:

Appearance:

Melting point: 208 C; 200.5 C

Optical rotation:

Solubility: 10.1 mg/ml (21C, in water)

logP: 1.35

pKa:
 

Stability:

 


1. DOYLE, F. P., NAYLER, J. H. C. & SMITH, H. British Patent Specification No. 873049, (1961).

2. BROWN, D. M. & ACRED, P. "Penbritin-a new broad-spectrum antibiotic". Brit. med. J. ii, 197-198, (1961).

3. ACRED P., BROWN D.M., TURNER D.H., WILSON M.J. "Pharmacology and chemotherapy of ampicillin--a new broad-spectrum penicillin". Br. J. Pharmacol. Chemother- 18: 35669, (1962).

 

 

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