Pharmacology: Pharmacodynamics Mechanism of Action:
Phenoxymethylpenicillin (Penicillin V) is a natural penicillin produced by fermentation of mutant strains of Penicillium chrysogenum
. It is usually bactericidal in action by interfering with the bacterial cell wall synthesis. Phenoxymethylpenicillin binds to penicillin-binding proteins on the bacterial cell wall and blocks peptidoglycan synthesis. Peptidoglycan is a heteropolymeric structure that gives the cell wall its mechanical stability. The final stage of peptidoglycan synthesis involves the completion of the cross-linking with the terminal glycine residue of the pentaglycine bridge linking to the fourth residue of the pentapeptide. The transpeptidase enzyme that performs this step is inhibited by penicillins. The bacterial cell wall is thus weakened, the bacterial cell swells and then ruptures.
In healthy, fasting adults, about 60 to 73% of an oral dose of phenoxymethylpenicillin is absorbed rapidly from the gastrointestinal (GI) tract.
Peak serum concentrations are reached within 30 to 60 minutes after a single oral dose of phenoxymethylpenicillin in fasting children or adults.
Single oral administration of phenoxymethylpenicillin 250 mg tablet in healthy, fasting adults results in serum drug concentrations averaging 2.1-2.8, 2.3-2.7, 0.8-0.9, and 0.1-0.2 µg/mL at 30 minutes, 1 hour, 2 hours, and 4 hours, respectively, after the dose. Single oral administration of phenoxymethylpenicillin 500 mg tablet in healthy, fasting adults results in serum drug concentrations averaging 4.7-5, 4.9-6.3, 2.3-3, and 0.04-0.1 μg/mL at 30 minutes, 1 hour, 2 hours, and 6 hours, respectively, after the dose.
Phenoxymethylpenicillin is readily distributed into ascetic, synovial, pleural, and pericardial fluids. The drug is widely distributed into body tissues with highest concentrations attained in the kidneys and lower amounts in the liver, skin, intestines, and muscle. Phenoxymethylpenicillin is also distributed into bile, tonsils, maxillary sinus secretions, and saliva in low concentrations. Minimal drug concentrations generally distribute into CSF in patients with uninflamed meninges. In general, only negligible amounts of natural penicillins are attained in avascular areas, abscesses, aqueous humor, sweat, team, or bone.
Phenoxymethylpenicillin readily crosses the placenta and is distributed into human milk. About 75% to 89% of the drug is bound to serum proteins.
The serum half-life of phenoxymethylpenicillin in adults with normal renal function is reportedly 0.5 hours. About 35% to 70% of the drug is metabolized to penicilloic acid which is microbiologically inactive. Small amounts of 6-aminopenicillanic acid (6-APA) have also been found in urine of patients receiving phenoxymethylpenicillin. In addition, the drug appears to be hydroxylated to a small extent to one or more microbiologically active metabolites.
Phenoxymethylpenicillin and its metabolites are excreted in urine mainly by tubular secretion. Small amounts of the drug are also excreted in feces and bile. After a single oral administration of phenoxymethylpenicillin in adults with normal renal function, 26% to 65% of the dose is excreted in urine as unchanged drug and metabolites within 6 to 8 hours; about 32% of the dose is excreted in feces. Renal clearance of phenoxymethylpenicillin is delayed in neonates, young infants, and patients with renal impairment. It is not known if the drug is removed by hemodialysis or peritoneal dialysis.
Microbiology: Antimicrobial Spectrum of Activity:
Phenoxymethylpenicillin is bactericidal against penicillin-sensitive microorganisms during the stage of active multiplication.
It has demonstrated activity in vitro
and in clinical infections against strains of the following microorganisms: (See Table 1.)
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Phenoxymethylpenicillin has also demonstrated in vitro
activity against some strains of the following microorganisms; however, clinical significance is unknown: (See Table 2.)
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