Amoxicillin trihydrate is a chemical compound, the trihydrate form of amoxicillin, a semisynthetic aminopenicillin (α-amino hydroxy benzylpenicillin) that binds to penicillin 1A binding protein by an acylation process. It has been in use since 1970.

Take only under medical supervision

The name describes the structure of the molecule:

• "Amoxicillin" is a semi-synthetic antibiotic, an analog of ampicillin, with a broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms.
• "Trihydrate" indicates that each molecule of amoxicillin is associated with three water molecules. This is a common form of the drug because it is stable and easy to manufacture and store.

The synthesis process takes place in different steps:

• The process starts with the reaction of phenylglycine with penicillin G, a natural penicillin, to produce 6-aminopenicillanic acid (6-APA), a key intermediate in the production of semisynthetic penicillins.
• The 6-APA is then acylated with an acid chloride derivative of p-hydroxyphenylglycine, a step that introduces the side chain that characterizes amoxicillin.
• The product of this reaction is amoxicillin, which is then treated with water to produce amoxicillin trihydrate.

Like all drugs it can cause side effects. Always ask the physician.

As a beta-lactam antibiotic, its efficacy depends on the length of time that serum free concentrations remain above the minimum inhibitory concentration during the dosing interval which means that differences in pharmacodynamic activity have implications for optimal dosing regimens (1).

Amoxicillin trihydrate is one of the most widely used antibiotics, with broad antibacterial spectrum, in current therapeutic regimens for the treatment of infections affecting:

• urinary tract
• respiratory tract
• ear and sinuses
• skin and soft tissues
• bones and joints
• teeth
• and other

Pharmacodynamics and pharmacokinetics have an important influence on the antimicrobial efficacy of many oral agents such as Amoxicillin trihydrate which offers a good safety profile even at high doses (2).

However, although Amoxicillin is widely used for the treatment of simple infections that are sensitive to penicillin, its use as a single drug is in many cases insufficient due to bacteria that produce beta-lactamase and are able to render Amoxicillin harmless. To overcome this drawback, Amoxicillin has long been combined with clavulanic acid which, even in small quantities, has the function of inhibiting beta-lactamase. Ratios for an amoxicillin-clavulanic acid combination range from 7:1 to 16:1 to avoid clavulanic acid-related toxicity (3)

A prospective double-blind controlled study positively evaluated the efficacy of amoxicillin trihydrate (which normally has no antistaphylococcal activity) with the addition of clavulanic acid in the treatment of nonbullous (contagious) impetigo caused by staphylococci (Gram-positive bacteria that are believed to cause even severe infections on soft tissues and skin) compared with the administration of Amoxicillin alone (4).

In another study referring to patients with postoperative complications and on patient comfort after mandibular third molar surgery, the results concluded that Amoxicillin trihydrate and Amoxicillin trihydrate with clavulanic acid could provide similar results in terms of patient comfort in the postoperative course (5).

The most relevant studies on this chemical compound have been selected with a summary of their contents:

Amoxicillin trihydrate studies

Optimal typical characteristics of the commercial product Amoxicillin trihydrate

Appearance	White crystalline powder
Density	1.54g/cm3
Melting Point	>200ºC (dec.)
Boiling Point	743.2ºC at 760 mmHg Vapour
Flash Point	403.3ºC
Refractive Index	302 ° (C=0.1, H2O)
PSA	185.95000
LogP	0.85990
Storage	2-8°C
Safety

• Molecular Formula: C₁₆H₂₅N₃O₈S
• Molecular Weight: 419.450
• CAS: 61336-70-7
• UNII 804826J2HU
• EC Number: 612-127-4
• DSSTox Substance ID: DTXSID2022599
• MDL number  MFCD00072029
• PubChem Substance ID 329823148
• InChl=1S/C16H19N3O5S.3H2O/c1-16(2)11(15(23)24)19-13(22)10(14(19)25-16)18-12(21)9(17)7-3-5-8(20)6-4-7;;;/h3-6,9-11,14,20H,17H2,1-2H3,(H,18,21)(H,23,24);3*1H2/t9-,10-,11+,14-;;;/m1.../s1  
• InChl Key      MQXQVCLAUDMCEF-CWLIKTDRSA-N
• SMILES    CC1(C(N2C(S1)C(C2=O)NC(=O)C(C3=CC=C(C=C3)O)N)C(=O)O)C.O.O.O
• IUPAC (2S,5R,6R)-6-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;trihydrate
• ChEBI    51254
• NACRES  NA.24
• Beilstein  7507120

Synonyms:

• 4-Thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 6-((amino(4-hydroxyphenyl)acetyl) amino)-3,3-dimethyl-7-oxo-, trihydrate, (2S-(2-alpha,5-alpha,6-beta(S*)))-
• Amoxicillin Anhydrous
• Amoxicillin, (R*)-isomer

References__________________________________________________________________

(1) Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998 Jan;26(1):1-10; quiz 11-2. doi: 10.1086/516284. 

(2) Jacobs MR. Building in efficacy: developing solutions to combat drug-resistant S. pneumoniae. Clin Microbiol Infect. 2004 Apr;10 Suppl 2:18-27. doi: 10.1111/j.1470-9465.2004.00862.x. 

(3) Huttner A, Bielicki J, Clements MN, Frimodt-Møller N, Muller AE, Paccaud JP, Mouton JW. Oral amoxicillin and amoxicillin-clavulanic acid: properties, indications and usage. Clin Microbiol Infect. 2020 Jul;26(7):871-879. doi: 10.1016/j.cmi.2019.11.028.

(4) Dagan R, Bar-David Y. Comparison of amoxicillin and clavulanic acid (augmentin) for the treatment of nonbullous impetigo. Am J Dis Child. 1989 Aug;143(8):916-8. doi: 10.1001/archpedi.1989.02150200068020. 

(5) Esen A. The effects of amoxicillin with or without clavulanic acid on the postoperative complaints after third molar surgery: a retrospective chart analysis. J Istanb Univ Fac Dent. 2017 Apr 3;51(2):1-6. doi: 10.17096/jiufd.53300. 

Compendium of the most significant studies with reference to properties, intake, effects.

Huttner A, Bielicki J, Clements MN, Frimodt-Møller N, Muller AE, Paccaud JP, Mouton JW. Oral amoxicillin and amoxicillin-clavulanic acid: properties, indications and usage. Clin Microbiol Infect. 2020 Jul;26(7):871-879. doi: 10.1016/j.cmi.2019.11.028. 

Abstract.  In this narrative review, we re-examine the properties of oral amoxicillin and clavulanic acid and provide guidance on their use, with emphasis on the preferred use of amoxicillin alone.

Todd PA, Benfield P. Amoxicillin/clavulanic acid. An update of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs. 1990 Feb;39(2):264-307. doi: 10.2165/00003495-199039020-00008.

Abstract. Clavulanic acid enhances the antibacterial spectrum of amoxicillin by rendering most beta-lactamase-producing isolates susceptible to the drug. In clinical trials amoxicillin/clavulanic acid is clinically and bacteriologically superior to amoxicillin alone and at least as effective as numerous other comparative agents, such as orally administered cephalosporins, cotrimoxazole, doxycycline and bacampicillin, in the treatment of adults and children with the most common forms of infection encountered in general practice, i.e. urinary tract infections, upper and lower respiratory tract infections, otorhinolaryngological infections, and skin and soft tissue infections.

Binson G, Grignon C, Le Moal G, Lazaro P, Lelong J, Roblot F, Venisse N, Dupuis A. Overcoming stability challenges during continuous intravenous administration of high-dose amoxicillin using portable elastomeric pumps. PLoS One. 2019 Aug 16;14(8):e0221391. doi: 10.1371/journal.pone.0221391.

Abstract. While treatment of serious infectious diseases may require high-dose amoxicillin, continuous infusion may be limited by lack of knowledge regarding the chemical stability of the drug. Therefore, we have performed a comprehensive study so as to determine the chemical stability of high-dose amoxicillin solutions conducive to safe and effective continuous intravenous administration using portable elastomeric pumps. 

Gras-Le Guen C, Boscher C, Godon N, Caillon J, Denis C, Nguyen JM, Kergueris MF, Roze JC. Therapeutic amoxicillin levels achieved with oral administration in term neonates. Eur J Clin Pharmacol. 2007 Jul;63(7):657-62. doi: 10.1007/s00228-007-0307-3.

Abstract.  We investigated whether effective serum amoxicillin concentrations could be reached by switching to oral amoxicillin after 48 h of intravenous administration in full-term neonates with group B Streptococcus infection.

Thombre NA, Gide PS. Floating-bioadhesive gastroretentive Caesalpinia pulcherrima-based beads of amoxicillin trihydrate for Helicobacter pylori eradication. Drug Deliv. 2016;23(2):405-19. doi: 10.3109/10717544.2014.916766.

Abstract.  An oral dosage form containing floating bioadhesive gastroretentive microspheres forms a stomach-specific drug delivery system for the treatment of Helicobacter pylori.

Wildermuth BE, Griffin CE, Rosenkrantz WS. Response of feline eosinophilic plaques and lip ulcers to amoxicillin trihydrate-clavulanate potassium therapy: a randomized, double-blind placebo-controlled prospective study. Vet Dermatol. 2012 Apr;23(2):110-8, e24-5. doi: 10.1111/j.1365-3164.2011.01020.x.

Abstract. In this study, we evaluated the treatment of feline eosinophilic plaques and lip ulcers with amoxicillin trihydrate-potassium clavulanate (Clavamox(®); Pfizer Animal Health). Nineteen cats with clinical and cytological findings consistent with eosinophilic plaques and/or lip ulcers were enrolled.