Augmentin - Clavulanic acid

Although a broad range of P-lactamase inhibitors has been discovered, only clavulanic acid and sulbactam have been commercialized. Clavulanic acid (12, R = CH2OH, R = H), manufactured by SmithKlinp Beecham, is sold as an oral and parenteral product in combination with amoxicillin under the trade name Augmentin. A parenteral product in combination with ticarcillin [34787-01-4], C25H2gN20 S, has the trade name, Timentin. In 1990 worldwide sales of clavulanic acid containing products were about 725 million. 

Aminopenicillins amoxicillin a-mox-i-sil -in amoxicillin and clavulanate acid a-mox-i-sil -in/ klah-view-lan -ate Amoxil, Trimox, Wymox, generic Augmentin Same as penicillin G Same as penicillin G... 

Of particular note is the combination of amoxicillin and clavulanic acid. The latter is a potent inhibitor of enzymes that degrade amoxicillin and many other p-lactam antibiotics. This combination, marketed as Augmentin, increases the efficacy of amoxicillin against organisms that would be otherwise resistant to it. It is among the most widely used antibiotics in the United States. 

Augmentin ES-600 - Augmentin ES-600, 600 mg/5 mL, does not contain the same amount of clavulanic acid (as the potassium salt) as any of the other Augmentin suspensions. Do not substitute Augmentin 200 mg/5 mL and 400 mg/5 mL suspensions for Augmentin ES-600, as they are not interchangeable. Dosage ... 

Augmentin tablets (250 or 500 mg) cannot be used to provide the same dosages as Aagmenf/V XR extended-release tablets. This is because Augmentin XR contains 62.5 mg clavulanic acid, while the Augmentin 250 and 500 mg tablets each contain 125 mg clavulanic acid. In addition, the extended-release tablet provides an P.859... 

Current commercial inhibitors of /3-lactamases include clavulanic acid (an oxapenam see Table 1), sulbactam, and tazobactam (two penam sulfones see Table 1). They are effective only against the class A serine /3-lactamases and they are administrated in the form of antibiotic/inhibitor combinations <2006BP930> Augmentin (amoxicillin/clavulanic acid), Timentin (ticarcillin/clavulanic acid), Unasyn (ampicillin/Sulbactam), Zosyn (piperacillin/tazobactam). 

Recently, prodrugs have been constmcted in which amoxicillin (antibacterial agent) and clavulanic acid or cephalosporin 1-oxide (/3-lactamase inhibitors) are covalently linked. All these compounds show better antibacterial activity than Augmentin , comparable anti-/3-lactamase activity, and better solubility properties <2002BMC3489>. 

Augmentin is a combination therapy where the bacterial resistance to penicillins is reduced by the use of the [3-lactamase inhibitor clavulanic acid (20). It originated from Beechams and is now marketed by GlaxoSmithKline (GSK). 

The natural penicillins, primarily G and V, have a relatively narrow spectrum. They act mostly on gram-positive organisms. The fact that proper selection of precursors could lead to new variations in the penicillin side chain offered the first source of synthetic penicillins. Penicillin V, derived from a phenoxy-acetic acid precursor, attracted clinical use because of its greater acid tolerance, which made it more useful in oral administration. Also, the widespread use of penicillin eventually led to a clinical problem of penicillin-resistant staphylococci and streptococci. Resistance for the most part involved the penicillin-destroying enzyme, penicillinase, which attacked the beta-lactam structure of the 6-aminopenicillanic acid nucleus (6-APA). Semisynthetic penicillins such as ampicillin and carbenicillin have a broader spectrum. Some, such as methicillin, orafi-cillin, and oxacillin, are resistant to penicillinase. In 1984, Beecham introduced Augmentin, which was the first combination formulation of a penicillin (amoxicillin) and a penicillinase inhibitor (clavulanic acid). Worldwide production of semisynthetic penicillins is currently around 10,000 tons/year, the major producers are Smith Kline Beecham, DSM, Pfizer, and Toyo Jozo. 

Carindapen , Geopen , Pyopen Clavulanic acid + amoxicillin Augmentin ... 

Clavulanic acid (80), isolated from Strepto-myces clavuligeruSy is similar in structure to the penicillins, except oxygen replaces sulfur in the five-membered ring (123). Clavulanic acid has weak antibacterial activity, but is a potent inhibitor of p-lactamases (124). A mixture of clavulanic acid and the j8-lactamase-sensitive amoxycillin was introduced in 1981 as Augmentin and has proved to be an effective combination to combat jS-lactamase-pro-ducing bacteria (125). In 2001,20 years after its launch, Augmentin is the best-selling antibacterial worldwide. 

The in vivo activity of a combination of clavulanic acid and amoxycillin is shown in Table 6.4 [30]. This -lactamase inhibitory activity, together with useful pharmacokinetic properties, has resulted in the development of Augmentin (potassium clavulanate in combination with amoxycillin) for oral and parenteral use and Timentin (potassium clavulanate plus ticarcillin) for parenteral use, against a wide range of bacterial infections. ... 

Clavulanic acid is manufactured by SmithKline Beecham and is sold as oral and parenteral products in combination with amoxycillin under the trade name of Augmentin, and as an injectable product in combination with ticarcillin under the trade name of Timentin. Augmentin is prescribed for infections of the respiratory tract such as bronchitis, and ear, nose and throat infections such as otitis media and sinusitis. It is also indicated for infections of the urinary tract, such as gonorrhoea, and skin and soft tissue infections, which include cellulitis, impetigo and abscesses. Timentin meanwhile is used for the treatment of severe infections in hospitalised patients with impaired or suppressed host defences. 

The discovery of clavulanic acid in 1976 heralded a new era in antibacterial chemotherapy. The enormous success of Augmentin (amoxycillin in combination with clavulanic acid) for the treatment of infections caused by /5-lactamase producing bacteria has established that /5-lactamase inhibitors have an important role to play in solving the problem of bacterial resistance. The widespread interest and enthusiasm created by the discovery of clavulanic acid has culminated in the development of two additional /5-lactamase inhibitors, namely, sulbactam and tazobactam. 

Strieker BH, Van den Broek JW, Keuning J, Eberhardt W, Houben HG, Johnson M, Blok AP. Cholestatic hepatitis due to antibacterial combination of amoxicillin and clavulanic acid (Augmentin) Dig Dis Sci 1989 34(10) 1576-80... 

Dowsett JF, Ghlow T, Heagerty A, RadcUffe M, Toadi R, Isle I, Russell RC. AmoxyciUin/clavulanic acid (Augmentin)-induced intrahepatic cholestasis. Dig Dis Sci 198934(8) 1290-3. 

Streptomyces clavuligerus. This was essentially devoid of antibacterial activity but was a very effective inhibitor of beta-lactamases produced by a wide variety of bacteria. Some idea of the excitement these results caused can be seen from Beecham s data for the minimum inhibitory dose of ampicillin needed for a typical resistant staphylococcus without clavulanic acid (500 fig ml-1) and with clavulanic acid (less than 0.4 fig ml-1)- Five years later, they were able to demonstrate that the combination of the broad-spectrum penicillin - amoxycillin - with clavulanic acid was very effective in clinical use. This combination was marketed as Augmentin and soon became one of the best-selling drugs in the world market. 

Augmentin/amoxillin plus clavulanic acid Anti-infective Enzyme inhibitor... 

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