Streptococci cannot grow when Penicillin V (0.002-8.0 mg/L) is present; its minimum inhibitory concentrations (MICs) are 0.004-0.008 mg/L[2]. With a MIC50 of 4.0 mg/L and a MIC90 of 8.0 mg/L, Penicillin V (0.002-8.0 mg/L) has antibacterial activity against Clostridium difficile[3]. MIC of 0.016 mg/L, penicillin V (0.004-0.063 mg/L; 18 h) inhibits the development of Staphylococcus aureus[4].

Penicillin V (0.063–0.25 mg/kg; sc) prevents S from growing. in the thigh muscle of mice[4]. Penicillin V (2 mg/kg; sc) had a mean AUC of 0.47 mg/L·h and a plasma half-life of 61 minutes[4]. Rats with acute purulent otitis media (AOM), a fulminant infection, are protected against by penicillin V (100 mg/kg; po once daily for 5 d)[5].

Animal/Disease Models: Specific pathogen free (SPF) male Swiss mice (20-25 g) are inoculated S. aureus[4]
Doses: 0.063, 0.13, 0.25 mg/kg
Route of Administration: Sc
Experimental Results: diminished the number of CFU (1.34×107 counts/mL) compared to controls (3.5×107 counts/mL) at the dose of 0.25 mg/kg.

Absorption, Distribution and Excretion
Upon oral administration, phenoxymethylpenicillin is rapidly but incompletely absorbed. The bioavailability of phenoxymethylpenicillin ranges from 25 to 60%. Compared to the free acid form of the drug, the calcium or potassium salts of phenoxymethylpenicillin displays better absorption profiles. It is reported that fasting state enhances the drug absorption. The peak plasma concentrations of 200 to 700 ng/mL are achieved in 2 hours following an oral dose of 125 mg. Following an oral dose of 500 mg, the peak plasma concentrations of 3 to 5 μg/mL are reached in 30 to 60 minutes post-dose.
While the drug is rapidly excreted, only 25% of the total dose is detected in the urine. Renal excretion may be delayed in neonates, young infants, and patients with renal impairment.
Following intravenous administration, the volume of distribution at steady state was 35.4 L. Small amounts of the drug can be found in various tissues, with the highest amount found in the kidneys, with lesser amounts in the liver, skin, and intes­ tines. Phenoxymethylpenicillin was found in the cerebrospinal fluid. Phenoxymethylpenicillin was detectable in the placenta and human breast milk.
A dose of 1,000,000 units of the acid gives peak plasma levels of about 2 to 3 ug/ml ...
Approx 60-73% of an oral dose of penicillin V or penicillin V potassium is absorbed from the GI tract in healthy, fasting adults. Following oral administration of a single dose of penicillin V or penicillin V potassium in fasting children or adults, peak serum concn of penicillin V are generally attained within 30-60 min. Peak serum penicillin V concn are attained sooner and are slightly higher following administration of the potassium salt than the free acid.
Following oral administration of a single 125-mg tablet of penicillin V potassium in healthy, fasting adults in one study, serum penicillin V concn averaged 1.2, 1.2, 0.5, and 0.1 ug/ml @ 30 min, 1 hr, 2 hr, and 4 hr, respectively, after the dose. Oral administration of a single 250-mg tablet of the drug in healthy, fasting adults results in serum penicillin V concn averaging 2.1-2.8, 2.3-2.7, 0.8-0.9, and 0.1-0.2 ug/ml @ 30 min, 1 hr, 2 hr, and 4 hr, respectively, after the dose. Following oral administration of a single 500-mg tablet of penicillin V potassium in healthy, fasting adults, serum penicillin V concn average 4.7-5, 4.9-6.3, 2.3-3, and 0.04-0.1 ug/ml @ 30 min, 1 hr, 2 hr, and 6 hr, respectively, after the dose.
Variable results have been obtained in studies evaluating the effect of food on GI absorption of penicillin V and penicillin V potassium. In most studies, presence of food in the GI tract resulted in lower and delayed peak serum concn of penicillin V, although the total amt of drug absorbed was unaffected. However, results of several studies in children 2 mo to 5 yr of age indicate that both the peak serum concn and the area under the serum concn-time curve (AUC) are decreased when penicillin V potassium is administered with or immediately prior to milk or food.
For more Absorption, Distribution and Excretion (Complete) data for PENICILLIN V (8 total), please visit the HSDB record page.

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Metabolism / Metabolites
About 35-70% of an oral 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.
Approximately 35-70% of an oral dose of penicillin V or penicillin V potassium is metabolized to penicilloic acid which is microbiologically inactive. Small amt of 6-aminopenicillanic acid (6-APA) have also been found in urine of patients receiving penicillin V. 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
Upon oral administration, the half-life is about 30 minutes. It can last up to 4 hours in patients with renal impairment.
The serum half-life of penicillin V in adults with normal renal function is reportedly 0.5 hr.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Limited information indicates that penicillin V 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 V is acceptable in nursing mothers.
◉ Effects in Breastfed Infants
In one study, 12 infants were breastfed during maternal penicillin V therapy. Seven appeared normal, 3 had looser stools than normal, and 1 had a rash on the buttocks on the last day of therapy. These effects were possibly related to penicillin V in milk, but no control group was present. One infant had stains of blood in the stool, but it had happened once prior to maternal penicillin V treatment.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Upon oral administration, about 50-80% of the drug is bound to plasma proteins.

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Interactions
Oral neomycin has been shown to decrease the absorption of penicillin V ... .
Since penicillin acts by inhibiting cell wall synthesis, agents which inhibit protein synthesis (eg, chloramphenicol) could ... mask the bactericidal effect of penicillin. /Penicillin/
Since penicillin acts by inhibiting cell wall synthesis, agents which inhibit protein synthesis (eg, erythromycin) could ... mask the bactericidal effect of penicillin. ... Clinical evidence exists for erythromycin-penicillin antagonism in patients with group A hemolytic streptococcal pharyngitis. ... The possibility of antagonism exists, but it has not been sufficiently documented in clinical studies. /Penicillin/
Tetracyclines ... may interfere with a bactericidal agent such as penicillin. /Penicillin/
For more Interactions (Complete) data for PENICILLIN V (16 total), please visit the HSDB record page.

[1]. Sabath LD. Et, al. Phenoxymethylpenicillin (penicillin V) and phenethicillin. Med Clin North Am. 1970 Sep;54(5):1101-11.
[2]. Kamme C, et, al. In vitro effect on group A streptococci of loracarbef versus cefadroxil, cefaclor and penicillin V. Scand J Infect Dis. 1993;25(1):37-42.
[3]. Norén T, et, al. In vitro susceptibility to 17 antimicrobials of clinical Clostridium difficile isolates collected in 1993-2007 in Sweden. Clin Microbiol Infect. 2010 Aug;16(8):1104-10.
[4]. Overbosch D, et, al. Comparative pharmacodynamics and clinical pharmacokinetics of phenoxymethylpenicillin and pheneticillin. Br J Clin Pharmacol. 1985 May;19(5):657-68.
[5]. Hermansson A, et, al. Prevention of experimental acute otitis media with penicillin V. Acta Otolaryngol. Jan-Feb 1990;109(1-2):119-23.
[6]. Timm A, et al. Photolysis of four β‑lactam antibiotics under simulated environmental conditions: Degradation, transformation products and antibacterial activity. Sci Total Environ. 2019 Feb 15;651(Pt 1):1605-1612.

Therapeutic Uses
Penicillins
Penicillin V is used for the treatment of mild to moderately severe infections caused by organisms susceptible to low concentrations of the drug or for prophylaxis of certain streptococcal infections.
Penicillin V /is/ indicated in the treatment of acute otitis media caused by susceptible organisms. /Included in US product labeling/
Penicillin V /is/ indicated in the treatment of bacterial pharyngitis cuased by susceptible organisms. /Included in US product labeling/
For more Therapeutic Uses (Complete) data for PENICILLIN V (21 total), please visit the HSDB record page.

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Drug Warnings
The most important biological effect of penicillin, unrelated to hypersensitivity or to "toxic" reaction, is alteration of bacterial flora in areas of the body to which it gains access. Regardless of the route by which the drug is administered, but most strikingly when it is given by mouth, penicillin changes the composition of the microflora by eliminating sensitive microorganisms. ... In some persons ... suprainfection results from the changes in flora. /Penicillin/
Fever and even vascular collapse and death may follow the use of penicillin in syphilis. This is one manifestation of the Jarisch-Herxheimer reaction. It is thought to be due to hypersensitivity to antigens released during rapid and massive lysis of spirochetes. /Penicillin/
Contraceptive failure and pregnancies attributed to the concurrent use of penicillins ... have been reported on a number of occasions. ... Mechanism /is/ not understood. It has been observed that ampicillin given to women in latter wk of pregnancy decreases urinary oestriol levels ... & phenoxymethylpenicillin behaves in a similar way ...
Individual with phenylketonuria (ie, homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine should be warned that Warner Chilcott's penicillin V potassium powder for oral soln contains aspartame ... which is metabolized in the GI tract to phenylalanine following oral administration.
For more Drug Warnings (Complete) data for PENICILLIN V (16 total), please visit the HSDB record page.

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Pharmacodynamics
Phenoxymethylpenicillin works against penicillin-sensitive microorganisms with bactericidal effects. It targets the bacteria during its active multiplication stage by interfering with bacterial cell wall peptidoglycan synthesis. _In vitro_, phenoxymethylpenicillin was shown to be active against staphylococci (except penicillinase-producing strains), streptococci (groups A, C, G, H, L and M), and pneumococci, as well as _Corynebacterium diphtheriae_, _Bacillus anthracis_, Clostridia, _Actinomyces bovis_, _Streptobacillus moniliformis_, _Listeria monocytogenes_, _Leptospira_, _Neisseria gonorrhoeae_, and _Treponema pallidum_.

C16H18N2O5S

350.39

350.093

87-08-1

Penicillin V Potassium;132-98-9;Penicillin V-d5;1356837-87-0

6869

white, crystalline powder

1.5±0.1 g/cm3

681.4±55.0 °C at 760 mmHg

120 - 128ºC

365.9±31.5 °C

0.0±2.2 mmHg at 25°C

1.651

1.88

2

6

5

24

547

3

C([C@H]1C(C)(C)S[C@@H]2[C@@H](C(N12)=O)NC(=O)COC1C=CC=CC=1)(=O)O

BPLBGHOLXOTWMN-MBNYWOFBSA-N

InChI=1S/C16H18N2O5S/c1-16(2)12(15(21)22)18-13(20)11(14(18)24-16)17-10(19)8-23-9-6-4-3-5-7-9/h3-7,11-12,14H,8H2,1-2H3,(H,17,19)(H,21,22)/t11-,12+,14-/m1/s1

4-Thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 3,3-dimethyl-7-oxo-6-((phenoxyacetyl)amino)-, (2S,5R,6R)-

CCRIS-752CCRIS752 CCRIS 752

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.)