Sultamicillin

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Sultamicillin
Sultamicillin.svg
Clinical data
Trade namesUnasyn, Unacid PD oral
AHFS/Drugs.comInternational Drug Names
Routes of
administration
By mouth
ATC code
Pharmacokinetic data
Bioavailability80%
ExcretionMainly via kidney
Identifiers
  • [(2R)-3,3-Dimethyl-4,4,7-trioxy-4λ6-thia-1-azabicyclo[3.2.0]heptane-2-carbonyl]oxymethyl(2R)-6-{[(2S)-2-amino-2-phenyl-acetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC25H30N4O9S2
Molar mass594.65 g·mol−1
3D model (JSmol)
  • O=C(OCOC(=O)[C@@H]2N1C(=O)C[C@H]1S(=O)(=O)C2(C)C)[C@@H]4N5C(=O)[C@@H](NC(=O)[C@@H](c3ccccc3)N)[C@H]5SC4(C)C
  • InChI=1S/C25H30N4O9S2/c1-24(2)17(29-20(32)16(21(29)39-24)27-19(31)15(26)12-8-6-5-7-9-12)22(33)37-11-38-23(34)18-25(3,4)40(35,36)14-10-13(30)28(14)18/h5-9,14-18,21H,10-11,26H2,1-4H3,(H,27,31)/t14-,15-,16-,17+,18+,21-/m1/s1 checkY
  • Key:OPYGFNJSCUDTBT-PMLPCWDUSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Sultamicillin, sold under the brand name Unasyn among others, is an oral form of the penicillin antibiotic combination ampicillin/sulbactam. It is used for the treatment of bacterial infections of the upper and lower respiratory tract, the kidneys and urinary tract, skin and soft tissues, among other organs. It contains esterified ampicillin and sulbactam.[1]

Sultamicillin is better absorbed from the gut than ampicillin/sulbactam, decreasing the chances of diarrhea and dysentery. The inclusion of sulbactam extends ampicillin's spectrum of action to beta-lactamase producing strains of bacteria.[2] Oral sulbactam with the intravenous form provides a regimen of continuous sulbactam therapy throughout the treatment, resulting in better clinical results.[citation needed]

It was patented in 1979 and approved for medical use in 1987.[3]

Medical uses

Medical uses for sultamicillin include:

Contraindications

Sultamicillin is contraindicated in people with penicillin allergy and those with mononucleosis, as these have an increased risk of developing severe rashes.[1][5]

Adverse effects

The most common side effect, as with many other antibiotics, is diarrhoea and soft stool. In Japanese clinical trials, these occurred with a frequency of 3.7% and 1.1%, respectively; however, in studies outside Japan, diarrhoea was much more common at 10& to over 50% in patients taking sultamicillin. Other adverse effects occurring in the range of 1 to 10% of people include nausea, vomiting, stomach ache, headache, rashes, and infections with Candida albicans. Haemorrhagic colitis caused by Clostridium difficile infections is a rare complication.[1][5]

Interactions

Interactions with other drugs are similar to other penicillins: allopurinol increases the risk for patients to develop rashes. Penicillins slow down the elimination of methotrexate, potentially increasing its adverse effects. Conversely, the elimination of sultamicillin's active constituents (ampicillin and sulbactam) is reduced by probenecid and probably by the nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin, indometacin and phenylbutazone.[1]

Pharmacology

Pharmacokinetics

The constituents of sultamicillin: ampicillin (blue), sulbactam (red), and the acylal link (black).

Sultamicillin is a codrug or (mutual prodrug) of ampicillin and sulbactam. After oral intake, it is absorbed and hydrolytically cleaved to ampicillin and sulbactam by enzymes in the gut wall. These two substances are then released into the system in a 1:1 molar ratio. Their pharmacokinetic behaviour is similar (and practically independent of food intake): they reach peak concentrations after about one hour; their plasma protein binding is 26% (ampicillin) and 29% (sulbactam); and their elimination half-lives are 45–80 minutes and 40–70 minutes, respectively. Both drugs are mainly eliminated via the kidneys: within eight hours after intake, 46 to 80% of the ampicillin and 41 to 66% of the sulbactam are found in the urine.[2][5]

Mechanism of action

Ampicillin, a semi-synthetic orally active broad-spectrum penicillin antibiotic, exerts antibacterial activity against sensitive organisms by inhibiting biosynthesis of cell wall mucopeptide. Sulbactam, a beta-lactamase inhibitor, irreversibly inhibits many beta-lactamases that occur in resistant bacteria strains.[1]

Chemistry

Ampicillin and sulbactam are linked via a methylene group, forming two ester bonds (or more accurately acylal bonds). Sultamicillin is used in form of the tosylate salt.[2][5]

References

  1. ^ a b c d e f g h i Haberfeld H, ed. (2020). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Unasyn-Filmtabletten.
  2. ^ a b c Mutschler E (2013). Arzneimittelwirkungen (in German) (10 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 745, 748. ISBN 978-3-8047-2898-1.
  3. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 491. ISBN 978-3-527-60749-5.
  4. ^ Mutschler E (2013). Arzneimittelwirkungen (in German) (10 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 790. ISBN 978-3-8047-2898-1.
  5. ^ a b c d Friedel HA, Campoli-Richards DM, Goa KL (April 1989). "Sultamicillin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use". Drugs. 37 (4): 491–522. doi:10.2165/00003495-198937040-00005. PMID 2661196.