Phenoxymethylpenicillin potassium

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics in vivo

Type of information:

other: Compilation and interpretation of available data.

Adequacy of study:

key study

Study period:

2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Compilation and interpretation of available data.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Objective of study:

absorption

distribution

excretion

metabolism

Qualifier:

equivalent or similar to guideline

Guideline:

other: Section R.7.12.2.1 of the 'Guidance on information requirements and chemical safety assessment'

Version / remarks:

2017

Deviations:

not specified

Principles of method if other than guideline:

Compilation and interpretation of available data.

GLP compliance:

no

Radiolabelling:

no

Details on absorption:

No relevant systemic toxic effects were noted in the acute oral and the acute inhalation toxicity studies.

Absorption: Approximately 25–73% of an oral dose of penicillin V absorbed from the GI tract in healthy, fasting adults. Peak serum concentrations attained within 30–60 minutes.
Variable results obtained in studies evaluating effect of food on GI absorption of penicillin V potassium. Food may result in lower and delayed peak serum concentrations, although the total amount of drug absorbed is unaffected.

In the acute inhalation toxicity study in rats with a MMAD of 3.65 µm did not show systemic toxic effects at the limit concentration of 5.24 mg/L, therefore no indication of an absorption was obtained. The relevant parameters for absorption at inhalation exposure are not very different to those for oral absorption, as described in the Section R.7.12.2.1 of the 'Guidance on information requirements and chemical safety assessment'.

Water Solubility: The substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis

Details on distribution in tissues:

Distribution: Widely distributed into body tissues. Highest concentrations in kidneys; lower concentrations in liver, skin, intestines, bile, tonsils, maxillary sinus secretions, saliva, and ascitic, synovial, pleural, and pericardial fluids. Only minimal amounts in CSF.
Crosses the human placenta and is distributed into human milk.

Bioaccumulation:
No relevant accumulation is expected, based on the low log Pow as wella as on the short half-life.

Transfer type:

blood/brain barrier

Observation:

distinct transfer

Remarks:

Plasma Protein Binding: Approximately 75–89%.

Details on excretion:

Elimination Route: Penicillin V and metabolites principally excreted in urine by tubular secretion. Approximately 26–65% of an oral dose excreted in urine as unchanged drug and metabolites within 6–8 hours; approximately 32% of the dose excreted in feces.
Serum half-life is 0.5 hours in adults with normal renal function..

Metabolites identified:

yes

Details on metabolites:

Metabolized in the liver. Approximately 35–70% of an oral dose is metabolized to penicilloic acid which is microbiologically inactive.

Conclusions:

Penicillin V (Penicillin V potassium, Phenoxymethyl penicillin, Phenoxymethylpenicillin Benzathine) oral and parenteral formulations indicated in the treatment of mild to moderately severe infections due to penicillin sensitive microorganisms. Penicillin V acts through the inhibition of biosynthesis of bacterial cell-wall mucopeptide. The doses and duration of treatment depends on microorganism and product formulation.
The most common reactions to oral penicillin are gastrointestinal effects and hypersensitivity reactions. Gastrointestinal reactions are mild diarrhea, nausea or vomiting. The hypersensitivity reactions reported are skin eruptions (maculopapular to exfoliative dermatitis), urticaria and other serum-sicknesslike reactions, laryngeal edema, and anaphylaxis.

Executive summary:

Absorption: Approximately 25–73% of an oral dose of penicillin V absorbed from the GI tract in healthy, fasting adults. Peak serum concentrations attained within 30–60 minutes.
Variable results obtained in studies evaluating effect of food on GI absorption of penicillin V potassium. Food may result in lower and delayed peak serum concentrations, although the total amount of drug absorbed is unaffected.
Distribution: Widely distributed into body tissues. Highest concentrations in kidneys; lower concentrations in liver, skin, intestines, bile, tonsils, maxillary sinus secretions, saliva, and ascitic, synovial, pleural, and pericardial fluids. Only minimal amounts in CSF.
Crosses the human placenta and is distributed into human milk.
Plasma Protein Binding: Approximately 75–89%.
Metabolized in the liver. Approximately 35–70% of an oral dose is metabolized to penicilloic acid which is microbiologically inactive.
Elimination Route: Penicillin V and metabolites principally excreted in urine by tubular secretion. Approximately 26–65% of an oral dose excreted in urine as unchanged drug and metabolites within 6–8 hours; approximately 32% of the dose excreted in feces.
Serum half-life is 0.5 hours in adults with normal renal function.
Special Populations: Renal clearance delayed in neonates, young infants, and individuals with renal impairment (FDA prescribing information, Penicillin V potassium tablets, oral solution)

Description of key information

Penicillin V (Penicillin V potassium, Phenoxymethyl penicillin, Phenoxymethylpenicillin Benzathine), a first generation penicillin, exerts a bactericidal action against penicillin-sensitive microorganisms during the stage of active multiplication. It acts through the inhibition of biosynthesis of cell-wall mucopeptide. Penicillin V oral (Penicillin V potassium, Phenoxymethyl penicillin) and parenteral (Phenoxymethylpenicillin Benzathine) formulations are indicated in the treatment of mild to moderately severe infections due to penicillin sensitive microorganisms. Penicillin V has been widely used in human medicine for several decades and has well defined safety profile.

Approximately 25–73% of an oral dose of penicillin V absorbed from the GI tract in healthy, fasting adults. Peak serum concentrations attained within 30–60 minutes.
Variable results obtained in studies evaluating effect of food on GI absorption of penicillin V potassium. Food may result in lower and delayed peak serum concentrations, although the total amount of drug absorbed is unaffected.
Distribution: Widely distributed into body tissues. Highest concentrations in kidneys; lower concentrations in liver, skin, intestines, bile, tonsils, maxillary sinus secretions, saliva, and ascitic, synovial, pleural, and pericardial fluids. Only minimal amounts in CSF.
Crosses the human placenta and is distributed into human milk.
Plasma Protein Binding: Approximately 75–89%.
Metabolized in the liver. Approximately 35–70% of an oral dose is metabolized to penicilloic acid which is microbiologically inactive.
Elimination Route: Penicillin V and metabolites principally excreted in urine by tubular secretion. Approximately 26–65% of an oral dose excreted in urine as unchanged drug and metabolites within 6–8 hours; approximately 32% of the dose excreted in feces.
Serum half-life is 0.5 hours in adults with normal renal function.

Penicillin V is generally well tolerated in humans but may occasionally cause transient nausea, diarrhoea and allergic reactions. It is well known that changes in the intestinal flora occur in all individuals treated orally with penicillin. The degree of alteration is related directly to the quantity administered. This effect is usually of no clinical significance and the normal microflora is re-established shortly after therapy is stopped.
For the penicillins, as a group, hypersensitivity reactions are the most common adverse effects noted, and penicillins are assumed to be the most common cause of drug allergy in humans. There is no convincing evidence that the single penicillin differs from the group in its potential for causing true allergic reactions, i.e. all penicillins are assumed to be cross-sensitizing and cross-reacting. The incidence of allergic reactions in connection with penicillin therapy varies from 0.7% to 10% in different studies. The major adverse effects of penicillins are acute anaphylaxis and collapse. Their incidence is thought to be 0.015 to 0.04% in humans treated with penicillin. Milder hypersensitivity reactions (urticaria, fever, angioneurotic edema) are more common. The overall prevalence of penicillin allergy in humans has been estimated to be between 3% and 10%.
From an occupational point of view sensitization and possible hypersensitivity reactions can occur at inhalation and dermal exposure. Furthermore it is generally accepted that especially relatively high peak concentrations can induce sensitization, and that prevention of such concentrations will prevent workers from developing respiratory allergy.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential