Phenoxymethylpenicillin

Structural formula
General
Non-proprietary name	Phenoxymethylpenicillin
other names	3,3-Dimethyl-7-oxo-6- (2-phenoxyacetamido) -4-thia-1-azabicyclo [3.2.0] heptane-2-carboxylic acid ( IUPAC ); Penicillin V;
Molecular formula	C 16 H 18 N 2 O 5 S
Brief description	white odorless powder
External identifiers / databases
EC number	201-722-0
ECHA InfoCard	100.001.566
PubChem	6869
ChemSpider	6607
DrugBank	DB00417
Wikidata	Q422215
Drug information
ATC code	J01 CE02
Drug class	β-lactam antibiotic
properties
Molar mass	350.39 g mol −1
Physical state	firmly
Melting point	120–128 ° C (decomposition)
pK s value	2.73
solubility	soluble in acetone and ethanol; practically insoluble in water;
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 302-317-334
	P: 261-280-342 + 311
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Phenoxymethylpenicillin , also known as penicillin V , there is known a prescription , bactericidal (germicidal) antibiotic of the family of penicillins ; it belongs to the active substance class of the β-lactam antibiotics and is β-lactamase-sensitive (= penicillinase-sensitive). Penicillin V is a narrow-spectrum penicillin and is mainly effective against certain streptococci and staphylococci , i.e. only against gram-positive pathogens.

History

Penicillin V was in 1951 when antibiotics manufacturers Biochemistry GmbH in Tyrolean Kundl discovered by researchers Ernst Brandl and Hans Margreiter and applied for a patent on April 22, the 1,952th It was the first penicillin, the orally could be administered. In the same year, it was first introduced in Austria a little later (distributed by the US pharmaceutical company Eli Lilly ) worldwide. In 1955 Karl Hermann Spitzy proved penicillin V to be the most effective among several acid-stable penicillins . Biochemie GmbH was later bought by Sandoz and still produces Penicillin V under the brand name Ospen . It has been approved in Switzerland since 1971. Penicillin V is also available as a generic .

Dosage form

Phenoxymethylpenicillin is usually sold orally as phenoxymethylpenicillin potassium , as a film-coated tablet, syrup and as a solution or dry substance for the preparation of a solution.

Pharmacokinetics

Phenoxymethylpenicillin is optimally about 60% absorbed in three quarters of an hour after passing through the stomach in the duodenum. Its absorption is reduced by simultaneous, especially high-fat food intake; correspondingly later, the therapeutically necessary penicillin V level in the blood is achieved or even not achieved. The absorption is also reduced in sprue and diarrheal diseases , it is increased with the additional administration of lactose and sucrose ; this is exploited by penicillin V producers in galenics: Penicillin V is z. B. sold with the addition of lactose monohydrate. Normally, the maximum plasma concentration is reached within one hour.

Penicillin V is more than half excreted via the kidneys in half an hour. The rest is metabolized to form the pharmacologically inactive penicilloylic acid . Six hours after oral administration, the phenoxymethylpenicillin plasma level has fallen to the point of therapeutic ineffectiveness. Phenoxymethylpenicillin penetrates the kidneys, lungs, liver, skin and mucous membranes well, but poorly penetrates muscles, bones, nerve tissue and the brain.

Area of application (indication)

A strict indication is essential, because resistance of the pathogens to u. a. Phenoxymethylpenicillins constitute the major and growing problem of healthcare-associated infections today ; therefore the therapeutic success must be checked by the doctor at short intervals. Before the penicillin V administration, a germ determination using a ' colored row ' and / or an antibiogram may have to be carried out; only in "classic" cases can and will not do so in the standard medical practice.

Phenoxymethylpenicillin should not be used together with tetracyclines , erythromycin or other macrolides , the bacteriostatic effect of the active ingredients opposes the bactericidal effect of penicillin V: Penicillin V only acts on dividing germs. It acts synergistically, i.e. enhancing its effect, to aminoglycosides and should only be combined with synergistically acting antibiotics.

The main areas of application are mild to moderate infections caused by gram-positive pathogens , including numerous anaerobic germs ( bacteria ). The bactericidal effect of phenoxymethylpenicillin can be used therapeutically against infections caused by β-hemolytic gram-positive streptococci of Lancefield group A ( Streptococcus pyogenes ); Phenoxymethylpenicillin inhibits the cell wall synthesis of the bacteria, the rapidly dividing bacteria can no longer build their cell wall ( murein ): they die. These infections include mainly throat and throat infections, such as B. the "classic" angina tonsillaris (streptococcal-induced tonsillitis, purulent tonsillitis), the "classic" erysipelas (streptococcal-induced red rash, rash), scarlet fever and rheumatic fever ; In 90% of cases, phenoxymethylpenicillin is also effective against dentogenic aerobic-anaerobic mixed infections (inflammation of the gums, etc.). The spectrum of activity is therefore quite narrow: only a few infections, typically caused by β-haemolytic streptococci of Lancefield group A, with these characteristic symptoms can usually be treated successfully in a short time - with indispensable control of the success; An antibiogram can be dispensed with in these cases.

As a prophylactic measure , phenoxymethylpenicillin can prevent sepsis lenta , (bacterial endocarditis ), rheumatic fever or chorea minor (Vitus dance) from attacking sepsis lenta , (bacterial endocarditis ), rheumatic fever or chorea minor (St. The streptococci of Lancefield groups C, G, H, L and M, which can be determined by means of a 'colorful row' or an antibiogram if necessary, prove to be highly sensitive to penicillin and thus also to phenoxymethylpenicillin.

Nose or ear infections are more often mixed infections of z. B. streptococci and other pathogens, especially the penicillin-insensitive Haemophilus influenzae , and are usually treated with more broadly effective antibiotics.

Streptococci of serogroup D ( enterococci ) are insensitive to (phenoxymethyl) penicillin .

Staphylococci are also sensitive to phenoxymethylpenicillin in the case of small-scale skin inflammation (small abscess , boils , impetigo contagiosa , circumscribed pyoderma , small phlegmon , erysipeloid ). However, staphylococci can produce penicillinase, an enzyme that breaks down penicillins, rendering them ineffective. As a rule, other, more broadly effective, especially penicillase-resistant antibiotics are used, if necessary penicillinase-resistant penicillins.

Pneumococci ( Streptococcus pneumoniae ), which can cause infections of the deep respiratory tract, such as in particular bacterial bronchitis or peribronchitis accompanied by yellowish to greenish sputum . budding bronchopneumonia , respond to penicillin V. As a rule, because of the possibility of a mixed infection with bacteria that are not sensitive to penicillin V (e.g. Haemophilus influenzae ), other, more broadly effective antibiotics are used. This rule does not apply to children with sickle cell anemia, who can receive prophylactic phenoxymethylpenicillin to protect against pneumococcal infection.

In the last two cases mentioned, obtaining an antibiogram ensures the successful use of phenoxymethylpenicillin, provided that penicillin V therapy is to be used in a targeted manner and that the pathogen can be clearly identified.

The mixed infection with spirochaetes and fusobacteria, which leads to the “classic” picture of the rarer Angina Plaut-Vincent , can be treated with phenoxymethylpenicillin; more broadly effective antibiotics are used.

Contraindications (contraindications)

Other gram-positive pathogens are also penicillin and theoretically sensitive to phenoxymethylpenicillin: Clostridia ( gas fire ), corynebacteria ( diphtheria ) and other, rarer germs such as. B. Bacillus anthracis ( anthrax ) or Listeria monocytogenes ( listeriosis ), against which in selected individual cases, with the use of antibiograms and with careful therapy monitoring carried out at short intervals, penicillins can be used, especially in high doses, but usually not phenoxymethylpenicillin; Depending on the cause of the infection, other antibiotics are used. Syphilis ( Treponema pallidum ) and gonorrhea pathogens ( Neisseria gonorrhoeae ) are special cases : The standard treatment for syphilis is still high-dose penicillin G therapy, whereas Neisseria gonorrhoeae have largely lost their sensitivity to penicillin today and are increasingly being treated against all other antibiotics resistant; both pathogens are therefore completely unsuitable for phenoxymethylpenicillin therapy. Penicillin V is largely obsolete in certain forms of borreliosis , for which it was still used a few years ago; here today other antibiotics come into play, especially and especially in the early forms of tetracyclines . Phenoxymethylpenicillin is ineffective against gram-negative pathogens: they only have a thin bacterial cell wall (murein).

Phenoxymethylpenicillin is by no means suitable for the treatment of severe infections (e.g. pneumococcal-induced severe acute bronchopneumonia), septicemia ( sepsis , bacteremia ) and in the presence of accumulations of pus in soft tissues ( abscess ) or body cavities ( empyema ). Phenoxymethylpenicillin is not indicated ( contraindicated ) in acute meningitis and acute arthritis , as well as in infections with streptococci of serogroup D ( enterococci ), which can trigger infections of internal organs , especially in immunocompromised infections. A successful (high-dose) penicillin G therapy can be replaced by an oral penicillin V therapy to end the antibiosis .

In veterinary medicine, Actinomyces bovis proves to be the causative agent of actinomycosis in cattle, at least in vitro, to be phenoxymethylpenicillin-sensitive.

Germs that are resistant to other oral penicillins and benzylpenicillin can also be resistant to phenoxymethylpenicillin; Strains that produce β-lactamase and are resistant to aminopenicillins, tetracyclines, erythromycin and chloramphenicol can also be resistant to phenoxymethylpenicillin. If these cross-resistance is present, phenoxymethylpenicillin is contraindicated.

Exclusively phenoxymethylpenicillin-resistant germs are all penicillinase-positive germs, germs from the order of the Enterobacteria (with the genera or species Enterobacter spp., Escherichia coli , Salmonella , Shigella , Serratia , Proteus mirabilis , Proteus vulgaris , Klebsiella pneumoniae ); furthermore Campylobacter fetus , Pseudomonadaceae , Haemophilus influenzae , enterococci (also: streptococci of serogroup D ), Brucella , Mycobacterium spp., Acinetobacter spp., Rickettsia spp., Mycoplasma spp .. They contraindicate phenoxymethylpenicillin administration.

The administration of phenoxymethylpenicillin in tablet form containing lactose (e.g. Ospen ^(R) film tablets ^{) is} contraindicated in patients with congenital galactose intolerance, glucose-galactose malabsorption or Lapp lactase deficiency.

Intolerance to penicillin V results in a relative, in severe cases an absolute contraindication for phenoxymethylpenicillin.

compatibility

Phenoxymethylpenicillin is generally well tolerated by toddlers and adults, but can range from relatively harmless allergic symptoms such as nettle rash (often) to acutely life-threatening, dramatic allergic reactions ( Quincke's edema , anaphylactic shock ) in 5–10% of cases. (very rarely) lead; the penicillin allergy represents a type 1 allergy or allergy of the immediate type ); A type IV allergy or allergy of the late type can rarely occur with a delay ; a clinical manifestation of the late type is the severe clinical picture of Steven-Johnson syndrome . Therefore, before administering penicillin V, you should always look for evidence of a penicillin allergy. Penicillin allergies can be caused in 1% of cases by foods containing penicillin. A cross allergy exists in 5–10% of all cases with hypersensitivity to cephalosporins . People with allergic diathesis (exogenous allergic bronchial asthma, allergic rhinitis (hay fever), urticaria) are more likely to develop a penicillin allergy. Overall, penicillin V-induced allergies are milder than those caused by penicillin G.

Other undesirable effects occur mainly after prolonged administration of the preparation; Here antibiotic-associated colitis and the development of resistance are to be mentioned first, as well as an increased tendency to fungal infections.

Other adverse renal ( interstitial nephritis ), haematological ( haemolytic anemia , leukopenia , eosinophilia, etc.) and hepatic (increase in liver enzymes ) reactions are rare to very rare . For long-term therapy with penicillin V, laboratory controls (blood count including differential blood count, liver and kidney function tests) are necessary.

Caution should be exercised when using phenoxymethylpenicillin, it can

In laboratory medicine, the non-enzymatic urine sugar test, the urobilinogen test and the amino acid determination in urine using the ninhydrin method are each false positive; the direct Coombs test can very rarely be positive
Oral contraceptives may become less effective, which may require the use of non-hormonal contraceptives
Penicillin V is inadvertently “administered” to the infant through breast milk while breastfeeding; The very small amount of medication that is conveyed usually has hardly any immediate effects, but can irritate the infant's intestinal flora (diarrhea, incorrect colonization by fungi) and sensitize him to penicillin
When using anti-inflammatory drugs, anti-inflammatory drugs, antipyretics such as indomethacin, salicylates in higher doses (against rheumatism), sulphinpyrazone, probenecid (against gout) and phenylbutazone (against arthrosis), an undesirably high increase in penicillin V in the serum can occur, because these take longer persistent and elevated penicillin V plasma levels as a result of competitive inhibition of excretion
in heart patients because of the increased intake of potassium to disturbances of the electrolyte and thus z. B. come to cardiac arrhythmias
in patients with kidney disease or the elderly due to possible renal insufficiency , if it is more pronounced, an undesirably high increase in penicillin V in the serum
skin changes and rashes are more likely to develop in people with acute lymphoblastic leukemia or glandular fever (mononucleosis); the risk of this is increased in these patients
If non-absorbable aminoglycosides are used for the purpose of intestinal sterilization (e.g. neomycin), penicillin absorption can be reduced

Teratogenic effects of phenoxymethylpenicillin, which crosses the placenta, are not known in humans. The roadworthiness is at most negligibly reduced, usually not restricted.

In very high doses, parenterally administered penicillins can trigger cerebral seizures , but usually not penicillin V.

Web links

Phenoxymethylpenicillin , Peer Reviewed Open Drug Database (German-speaking, Switzerland), accessed on August 2, 2012
Description of phenoxymethylpenicillin (including a detailed list of products and prices for Germany) , Onmeda (information distributed over several web pages!), Accessed on August 2, 2012
Antibiotics: Classification, Pharmacokinetics and Side Effects (Dr. Dr. Matthias Kelker) , IMC Wiki (International Medical College) (overview), accessed on August 1, 2012
Description of Penicillin V Potassium (penicillin v potassium) Powder, For Solution Bristol-Myers Squibb Company, accessed August 1, 2012
Description of the phenoxmethylpenicillin commercial preparation Ospen ^(R) 1 ME (Sandoz, detailed doctor and patient information; PDF; 66 kB), accessed on August 1, 2012
Description for a generic phenoxymethylpenicillin , Ratiopharm ^(R) (patient information), accessed August 1, 2012

Individual evidence

↑ ^a ^b ^c ^d ^e Entry on phenoxymethylpenicillin. In: Römpp Online . Georg Thieme Verlag, accessed on June 14, 2014.
↑ ^a ^b Data sheet Penicillin V potassium salt, VETRANAL at Sigma-Aldrich , accessed on May 14, 2017 ( PDF ).
↑ Narrow Spectrum Antibiotics , accessed May 14, 2017.
^ Tiroler Landesmuseum, On the history of the discovery of penicillin V in Kundl (Tyrol) (PDF; 4.9 MB).
^ Karl Hermann Spitzy : The history of the first acid-stable oral penicillin (penicillin V) . In: Antibiotikamonitor 16 (2000) 3, accessed on July 31, 2012
↑ From acid-resistant penicillin to high dosage , Univ.-Prof. GDR. Karl Hermann Spitzy over 40 years of antibiotic therapy ( Memento from October 29, 2013 in the Internet Archive ), Medical Tribune 40 (2008) 50-52, 30-31, accessed on July 31, 2012.
↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t Sandoz: Description of the phenoxmethylpenicillin commercial preparation Ospen ^(R) 1 ME (PDF; 66 kB) (detailed doctor and patient information, accessed on 1 August 2012).
↑ Entry on phenoxymethylpenicillin in Pharmawiki , accessed on August 1, 2012.
↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ detailed description of phenoxymethylpenicillin (including a detailed list of preparations and prices for Germany) ( Memento from January 3, 2012 in the Internet Archive ), Onmeda (information divided over several web pages! ), accessed August 2, 2012.
↑ ^a ^b ^c ^d ^e Description of a generic phenoxymethylpenicillin ( memento of October 29, 2013 in the Internet Archive ), Ratiopharm ^(R) , accessed on August 1, 2012.
↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t Phenoxymethylpenicillin , Peer Reviewed Open Drug Database (German-speaking, Switzerland), accessed on August 2, 2012
↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o Description of Penicillin V Potassium (penicillin v potassium) Powder, For Solution Bristol-Myers Squibb Company, accessed August 1, 2012.
↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j Antibiotics: Classification, Pharmacokinetics and Side Effects => Phenoxymethylpenicillin (Dr. Dr. Matthias Kelker) , IMC Wiki (International Medical College), accessed on August 1, 2012.
↑ ^a ^b Entry on phenoxymethylpenicillin in Flexikon , a Wiki of the DocCheck company , accessed on August 2, 2012.
↑ The antibiotic therapy of acute bronchitis is controversially discussed in medicine. Therapy of acute bronchitis .
↑ G. Stanek: Lyme borreliose: Diagnostic-therapeutic protocol for practice. 16 (2000) 3, accessed August 2, 2012.
↑ Entry on actinomycosis in cattle in Flexikon , a wiki from DocCheck , accessed on August 2, 2012.
↑ ^a ^b Entry on penicillin allergy in the Roche Medical Lexicon , accessed on August 2, 2012.
↑ "In the case of penicillin allergy, a normal spec. IgE does not exclude another allergy (e.g. type IV), ... “ , to: Allergy diagnostics => specific IgE, Institute for Clinical Chemistry, University of Mannheim, accessed on August 2, 2012.

[Römpp-1] Entry on phenoxymethylpenicillin. In: Römpp Online . Georg Thieme Verlag, accessed on June 14, 2014.

[Sigma-2] Data sheet Penicillin V potassium salt, VETRANAL at Sigma-Aldrich , accessed on May 14, 2017 ( PDF ).

[3] Narrow Spectrum Antibiotics , accessed May 14, 2017.

[4] Tiroler Landesmuseum, On the history of the discovery of penicillin V in Kundl (Tyrol) (PDF; 4.9 MB).

[5] Karl Hermann Spitzy : The history of the first acid-stable oral penicillin (penicillin V) . In: Antibiotikamonitor 16 (2000) 3, accessed on July 31, 2012

[6] From acid-resistant penicillin to high dosage , Univ.-Prof. GDR. Karl Hermann Spitzy over 40 years of antibiotic therapy ( Memento from October 29, 2013 in the Internet Archive ), Medical Tribune 40 (2008) 50-52, 30-31, accessed on July 31, 2012.

[Sandoz-7] ↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t Sandoz: Description of the phenoxmethylpenicillin commercial preparation Ospen ^(R) 1 ME (PDF; 66 kB) (detailed doctor and patient information, accessed on 1 August 2012).

[8] Entry on phenoxymethylpenicillin in Pharmawiki , accessed on August 1, 2012.

[Onmeda-9] ↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ detailed description of phenoxymethylpenicillin (including a detailed list of preparations and prices for Germany) ( Memento from January 3, 2012 in the Internet Archive ), Onmeda (information divided over several web pages! ), accessed August 2, 2012.

[frei-10] Description of a generic phenoxymethylpenicillin ( memento of October 29, 2013 in the Internet Archive ), Ratiopharm ^(R) , accessed on August 1, 2012.

[Database-11] ↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t Phenoxymethylpenicillin , Peer Reviewed Open Drug Database (German-speaking, Switzerland), accessed on August 2, 2012

[Myers-12] ↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o Description of Penicillin V Potassium (penicillin v potassium) Powder, For Solution Bristol-Myers Squibb Company, accessed August 1, 2012.

[IMC-13] ↑ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j Antibiotics: Classification, Pharmacokinetics and Side Effects => Phenoxymethylpenicillin (Dr. Dr. Matthias Kelker) , IMC Wiki (International Medical College), accessed on August 1, 2012.

[Flexicon-14] Entry on phenoxymethylpenicillin in Flexikon , a Wiki of the DocCheck company , accessed on August 2, 2012.

[15] The antibiotic therapy of acute bronchitis is controversially discussed in medicine. Therapy of acute bronchitis .

[16] G. Stanek: Lyme borreliose: Diagnostic-therapeutic protocol for practice. 16 (2000) 3, accessed August 2, 2012.

[17] Entry on actinomycosis in cattle in Flexikon , a wiki from DocCheck , accessed on August 2, 2012.

[PenAll-18] Entry on penicillin allergy in the Roche Medical Lexicon , accessed on August 2, 2012.

[19] "In the case of penicillin allergy, a normal spec. IgE does not exclude another allergy (e.g. type IV), ... “ , to: Allergy diagnostics => specific IgE, Institute for Clinical Chemistry, University of Mannheim, accessed on August 2, 2012.