Absorption, Distribution and Excretion
Rapidly absorbed following both intramuscular and subcutaneous injection. Initial blood levels following parenteral administration are high but transient. Oral absorption in fasting, healthy humans is only about 15-30% as it is very susceptible to acid-catalyzed hydrolysis.
Penicillin G is eliminated by the kidneys. Nonrenal clearance includes hepatic metabolism and, to a lesser extent, biliary excretion.
0.53–0.67 L/kg in adults with normal renal function
560ml/min in healthy humans
...WIDELY DISTRIBUTED THROUGHOUT BODY... ITS APPARENT VOL OF DISTRIBUTION IS IN ABOUT 50% OF TOTAL BODY WATER. MORE THAN 90%...IN BLOOD IS IN PLASMA & LESS THAN 10% IS IN ERYTHROCYTES; APPROX 65% IS REVERSIBLY BOUND TO PLASMA ALBUMIN. LOW CONCN OF PROTEIN...LOW DEGREE OF BINDING...DRUG EFFICACY.
SIGNIFICANT AMT APPEAR IN LIVER, BILE, KIDNEY, SEMEN, LYMPH, & INTESTINE. ... PENICILLIN DOES NOT READILY ENTER CSF WHEN MENINGES ARE NORMAL.
ORAL DOSES OF 500 MG POTASSIUM PENICILLIN G TO HUMAN SUBJECTS RESULT IN URINARY CONCN OF 600 UG/ML, FOR 2 HR, & 300 UG/ML, FOR 4 HR AFTER DOSING. ... INEFFICIENT PLACENTAL TRANSFER IS CONSISTENT WITH LOW LIPID SOLUBILITY & LOW IONIZATION CONSTANT OF PENICILLIN G & THERE IS NO EVIDENCE OF PLACENTAL TRANSPORT.
...RAPIDLY ELIMINATED FROM BODY, MAINLY BY KIDNEY BUT IN SMALL PART IN BILE & BY OTHER CHANNELS. ... CLEARANCE VALUES ARE CONSIDERABLY LOWER IN NEONATES & INFANTS, BECAUSE OF INCOMPLETE DEVELOPMENT OF RENAL FUNCTION...
For more Absorption, Distribution and Excretion (Complete) data for PENICILLIN G (21 total), please visit the HSDB record page.

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Metabolism / Metabolites
About 16-30% of an intramuscular dose is metabolized to penicilloic acid, an inactive metabolite. Small amounts of 6-aminopenicillanic acid have been recovered in the urine of patients on penicillin G. A small percentage of the drug appears to be hydroxylated into one or more active metabolites, which are also excreted via urine.
Approx 16-30% of an IM dose of penicillin G sodium is metabolized to penicilloic acid which is microbiologically inactive. Small amt of 6-aminopenicillanic acid (6-APA) have also been found in the urine of patients receiving penicillin G. In addition, the drug appears to be hydroxylated to a small extent to one or more microbiologically active metabolites which are also excreted in urine.

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Biological Half-Life
In adults with normal renal function is reportedly 0.4–0.9 hours
ELIMINATION HALF-LIFE IS ABOUT 30 MIN IN NORMAL ADULTS.
PENICILLIN HALF-LIFE IN HUMAN SERUM INCR FROM ABOUT 25 MIN IN YOUNG ADULTS TO 2 HR IN ELDERLY SUBJECTS & IS ALSO MARKEDLY INCR BY DRUGS WHICH ARE ACTIVELY SECRETED BY KIDNEY TUBULES. /PENICILLIN/
The serum half-life of penicillin G in adults with normal renal function is reportedly 0.4-0.9 hr.
The serum half-life of penicillin G in neonates varies inversely with age and appears to be independent of birthweight. The serum half-life of the drug is reportedly 3.2-3.4 hr in neonates 6 days of age or younger, 1.2-2.2 hr in neonates 7-13 days of age, and 0.9-1.9 hr in neonates 14 days of age or older.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Limited information indicates that penicillin G 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. Penicillin G is acceptable in nursing mothers.
◉ Effects in Breastfed Infants
A breastfed 1-month-old infant with congenital syphilis developed a Herxheimer reaction 6 hours after its mother received 2.4 million units of benzathine penicillin G intramuscularly. However, the baby had also received 10 units of penicillin G at about the same time as the mother's injection. The reaction was possibly caused by penicillin in breastmilk.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Bind to serum proteins (45-68%), mainly albumin.

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Interactions
MARKED POTENTIATION OF HYPOPROTHROMBINEMIC EFFECT OF WARFARIN BY LARGE DOSES OF PARENTERAL PENICILLIN G DESCRIBED IN 49-YR-OLD MALE. PENICILLIN G CAUSED WARFARIN PROTEIN BINDING DISPLACEMENT INTERACTION.
Penicillins are generally inactivated in the presence of heat, alkaline or acid pH, oxidizing agents, alcohols, glycols, and metal ions such as copper, mercury, or zinc. In currently available penicillins, cleavage at any point in the penicillin nucleus, including the beta-lactam ring, results in complete loss of antibacterial activity. The major cause of inactivation of penicillins is hydrolysis of the beta-lactam ring. The course of hydrolysis and nature of the degradation products can vary and are generally influenced by pH. /Penicillins/
Penicillin G is potentially physically and/or chemically incompatible with some drugs, including aminoglycosides and tetracyclines, but the compatibility depends on several factors (eg, concn of the drugs, specific diluents used, resulting pH, temp).
Penicillins are generally inactivated in the presence of heat, alkaline or acid pH, oxidizing agents, alcohols, glycols, and metal ions such as copper, mercury, or zinc. In currently available penicillins, cleavage at any point in the penicillin nucleus, including the beta-lactam ring, results in complete loss of antibacterial activity. The major cause of inactivation of penicillins is hydrolysis of the beta-lactam ring. The course of hydrolysis and nature of the degradation products can vary and are generally influenced by pH. /Penicillins/
For more Interactions (Complete) data for PENICILLIN G (18 total), please visit the HSDB record page.

Therapeutic Uses
Convulsants; GABA Modulators; Penicillins
GINGIVOSTOMATITIS, PULMONARY INFECTIONS, & GENITAL DISEASE PRODUCED BY SYNERGISTIC ACTION OF FUSOBACTERIUM NUCLEATUM (FUSIFORM) & SPIROCHETES PRESENT IN RESPIRATORY TRACT ARE READILY TREATABLE WITH PENICILLIN. /PENICILLIN/
TWO MICROORGANISMS RESPONSIBLE FOR.../RAT-BITE FEVER/ ARE SENSITIVE TO PENICILLIN G. ...DRUG OF CHOICE IN MGMNT OF INFECTIONS DUE TO LIST MONOCYTOGENES... ONLY SPECIES OF PASTEURELLA HIGHLY SUSCEPTIBLE TO PENICILLIN IS PAST MULTOCIDA. ... CAUSATIVE AGENT OF /ERYSIPELOID/...IS SENSITIVE TO PENICILLIN.
PENICILLIN G THERAPY OF SYPHILIS IS ALMOST IDEALLY SAFE, INEXPENSIVE, & HIGHLY EFFECTIVE. ...AGENT OF CHOICE FOR TREATMENT OF ALL CLINICAL FORMS OF ACTINOMYCOSIS...ANTHRAX...GAS GANGRENE...
For more Therapeutic Uses (Complete) data for PENICILLIN G (35 total), please visit the HSDB record page.

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Drug Warnings
WHEN MASSIVE DOSES OF PENICILLIN G SODIUM ARE USED, CONSIDERABLE SODIUM LOAD IS INTRODUCED, WHICH EXPANDS EXTRACELLULAR SPACE & MAY CAUSE EDEMA IN PT WITH HEART FAILURE. /PENICILLIN G SODIUM/
ALLERGIES CAN OCCUR TO PROCAINE COMPONENT, BUT OTHER TOXIC EFFECTS OF PROCAINE ARE VERY RARE. /PROCAINE/
ANURIA INCR HALF-LIFE OF PENICILLIN G FROM NORMAL VALUE OF 1/2 HR TO ABOUT 10 HR.
ALTHOUGH PENICILLIN G PREPN FOR INHALATION THERAPY & FOR TOPICAL APPLICATION TO SKIN & MUCOUS MEMBRANES ARE STILL AVAIL, THEIR USE IS NOT RECOMMENDED BECAUSE PROOF THAT THEY ARE ADEQUATELY EFFECTIVE IS LACKING, & BECAUSE THEY PRODUCE HIGH INCIDENCE OF HYPERSENSITIZATION.
For more Drug Warnings (Complete) data for PENICILLIN G (23 total), please visit the HSDB record page.

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Pharmacodynamics
Penicillin G 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. Penicillin G has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of penicillin G results from the inhibition of cell wall synthesis and is mediated through penicillin G binding to penicillin binding proteins (PBPs). Penicillin G is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases.

C16H18N2O4S

334.4

334.098

61-33-6

Penicillin G potassium;113-98-4;Penicillin G sodium salt;69-57-8;Streptomycin;57-92-1;Penicillin G procaine hydrate;6130-64-9;Penicillin G benzathine;1538-09-6;Penicillin G benzathine tetrahydrate;41372-02-5;Penicillin G-d7 potassium;352323-25-2

5904

AMORPHOUS WHITE POWDER

1.4±0.1 g/cm3

663.3±55.0 °C at 760 mmHg

214-217 °C
214 - 217 °C

355.0±31.5 °C

0.0±2.1 mmHg at 25°C

1.655

1.67

2

5

4

23

530

3

CC1([C@@H](N2C([C@@H](NC(CC3=CC=CC=C3)=O)[C@H]2S1)=O)C(O)=O)C

JGSARLDLIJGVTE-MBNYWOFBSA-N

InChI=1S/C16H18N2O4S/c1-16(2)12(15(21)22)18-13(20)11(14(18)23-16)17-10(19)8-9-6-4-3-5-7-9/h3-7,11-12,14H,8H2,1-2H3,(H,17,19)(H,21,22)/t11-,12+,14-/m1/s1

(2S,5R,6R)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

Galofak CilopenBenzylpenicillin Pradupen

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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.

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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).

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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)

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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).

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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

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)