Phenoxymethylpenicillin, commonly known as penicillin V, was introduced in 1953  and is an orally active penicillin antibiotic. It is less active than benzylpenicillin (penicillin G) against Gram-negative bacteria [2-3]. Phenoxymethylpenicillin is more acid-stable than benzylpenicillin, which allows it to be given orally. It exerts a bactericidal action against penicillin-sensitive microorganisms during the stage of active multiplication. It acts by inhibiting the biosynthesis of cell-wall peptidoglycan. It is not active against b-lactamase-producing bacteria, which include many strains of staphylococci.
In table 1 is reported the antibacterial activity of phenoxymethylpenicillin against several bacterial pathogens.
Table 1. In vitro susceptibility (MIC, mg/ml) to phenoxymethylpenicillin.
For the treatment of mild to moderately severe infections (e.g. dental infection, infections in the heart, middle ear infections, rheumatic fever, scarlet fever, skin infections, upper and lower respiratory tract infections) due to microorganisms.
Phenoxymethylpenicillin is usually used only for the treatment of mild to
moderate infections, and not for severe or deep-seated infections since
absorption can be unpredictable. Except for the treatment or prevention of
infection with Streptococcus pyogenes (which is uniformly sensitive to
penicillin), therapy should be guided by bacteriological studies (including
sensitivity tests) and by clinical response. Patients treated initially with
parenteral benzylpenicillin may continue oral treatment with
phenoxymethylpenicillin once a satisfactory clinical response has been obtained.
Dosage and Administration
Pen V is available as 125-, 250- and 500-mg capsules or tablets, and as a pediatric syrup, 125 or 250 mg in 5 ml. These drugs are administered orally, with the usual dose for adults of 250–500 mg administered every 6hours. The drugs should be given when fasting, preferably about 1 hour before meals. Higher doses may be used for the treatment of more serious infections.
Several studies have shown that oral penicillin V is effective in streptococcal pharyngitis and bacterial upper respiratory tract infections if the total daily dose is administered in two divided doses instead of three or four divided doses [4-6]. Persistence of carriage is a deﬁnite concern after penicillin treatment. There is speculation that this can be due to tolerance or co-pathogenicity due to b-lactamase production by the commensal upper respiratory tract ﬂora. More b-lactamase-stable agents, such as cephalosporins, probably offer an advantage if eradication is considered important.
Newborn infants and children
The pediatric syrup contains 125 or 250 mg in 5 ml. The Pen V dosage for children under ﬁve years is 125 mg four times a day, and for children over ﬁve years is the same as for adults, 250–500 mg every 6-hours. In one study in children, 250 mg of Pen V given twice daily was found to be equally as effective as 250 mg given three times daily for the treatment of streptococcal pharyngitis .
Dosage adjustments are rarely needed, unless substantial renal impairment is noted.
Phenoxymethylpenicillin is usually well tolerated but may occasionally cause transient nausea, vomiting, epigastric distress, diarrhea, and black hairy tongue. A previous hypersensitivity reaction to any penicillin is a contraindication.
Transient disturbances, such as nausea and diarrhea, can follow administration of these drugs. Candidiasis may also occur. Pseudomembranous colitis developed in one 12-year-old girl following a 4-day course of oral phenoxymethylpenicillin [8-9].
These may occur in penicillin-sensitive patients. Phenoxypenicillins may be cross-allergenic with penicillin G and also with all other penicillins and include both anaphylaxis and serum sickness. Anaphylaxis is much less common with the oral phenoxypenicillins than with parenteral Pen G. In one patient, symptoms started 30 minutes after ingestion of 500 mg of penicillin V . In another patient, generalized pruritus and ﬂushing commenced within 3 minutes of ingestion of a tablet of penicillin V. This was followed by abdominal cramps, nausea, and vomiting; she received medical treatment 30 minutes after the dose when she was semiconscious, cyanosed with tachycardia and hypotension. She responded to standard resuscitative measures . Serum sickness reactions are similar to those which occur after penicillin G.
Oral penicillins are of low toxicity, but massive doses, like those used with penicillin G, have not been administered to humans. Penicillin V is well tolerated in doses of up to 6 g/day.
One adult patient developed liver damage as part of a severe hypersensitivity reaction to penicillin V .
Phenoxypenicillin, like penicillin G, diffuse readily into pleural, pericardial, ascitic, and synovial ﬂuids and pass into the fetal circulation. There is very little penetration of phenoxypenicillin into the CSF if the meninges are uninﬂamed. Penicillin V penetrates poorly into maxillary sinus secretions . In inﬂamed tonsillar tissue, the concentration is about 20% of the serum level at that time .
About 20–40% of a given dose can be recovered from urine during the ﬁrst 6 hours. The drugs are mainly excreted unchanged, but small amounts of antibacterially active breakdown products are also present in the urine . Renal tubular secretion of phenoxypenicillin can be partially blocked by probenecid. Only small amounts are excreted in the bile, mainly in the unchanged form.
Mechanism of Action
By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, penicillin V 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.
Other pharmacological effects
CAS number: 87-08-1 EINECS:
Molecular Formula: C16H18N2O5S
Average mass: 350.39 Da
Monoisotopic mass: 350.093642386 Da
Systematic name: (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
Std. 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
1. Spitzy K.H. Wein Klin. Wschr. 65: 583, (1953).
2. Garrod, L. P. "Relative Antibacterial Activity of Three Penicillins". British Medical Journal 5172: 527–29, (1960).
3. Garrod, L. P. "The Relative Antibacterial Activity of Four Penicillins". British Medical Journal 5214: 1695–6, (1960).
4. Gerber M.A., Markowitz M. "Management of streptococcal pharyngitis reconsidered". Pediatr. Infect. Dis. 4: 518, (1985).
5. Fyllingen G., Arnesen A.R., Biermann C. et al.. "Phenoxymethylpenicillin two or three times daily for tonsillitis with beta-haemolytic streptococci Group A: a blinded, randomized and controlled clinical sudy". Scand. J. Infect. Dis. 23: 553, (1991).
6. Fyllingen G., Arnesen A.R., Ronnevig J. "Phenoxymethylpenicillin two or three times daily in bacterial upper respiratory tract infections: a blinded, randomized and controlled clinical study". Scand. J. Infect. Dis. 23: 755, (1991).
7. Gerber M.A., Spadaccini L.J., Wright L.L. et al.. "Twice-daily penicillin in the treatment of streptococcal pharyngitis". Am. J. Dis. Child. 139: 1145, (1985).
8. Larson H.E., Parry J.V., Price A.B. et al.. "Undescribed toxin in pseudomembranous colitis". Br. Med. J. 1: 1246, (1977).
9. Barrison I.G., Kane S.P. "Penicillin-associated colitis". Lancet 2: 843, (1978).
10. Coates W.H. "Anaphylactic shock following the administration of oral penicillin". Med. J. Aust. 1: 967, (1963).
11. Simmonds J., Hodges S., Nicol F., Barnett D. "Anaphylaxis after oral penicillin". Br. Med. J. 2: 1404, (1978).
12. Bird G.W.G., McEvoy M.W., Wingham J. "Acute haemolytic anaemia due to IgM penicillin antibody in a 3-year-old child: a sequel to oral penicillin". J. Clin. Path. 28: 321, (1975).
13. Beeley L., Gourevitch A., Kendall M.J. "Jaundice after oral penicillin". Lancet 2: 1297, (1976).
14. Lundberg C., Malmborg A.S. "Concentration of penicillin V and tetracycline in maxillary sinus secretion after repeated doses". Scand. J. Infect. Dis. 5: 123, (1973).
15. Roos K., Grahn E., Ekedahl C., Holm S.E. "Pharmacokinetics of phenoxymethylpenicillin in tonsils". Scand. J. Infect. Dis. 18: 125, (1986).
16. Bond J.M., Lightbown J.W.,
Barber M., Waterworth P.M. "A comparison of four phenoxypenicillins". Br.
Med. J. 2: 956, (1963).
Send mail to
questions or comments about this web site.