**2. Amoxicillin**

Originally introduced in the early 1970´s for oral use in United Kingdom, this drug has found gradually a regular place as a broad-spectrum antibiotic. In 1981, SmithKline Beecham patented amoxicillin/clavulanate potassium tablets, and first sold the antibiotic in 1998 under the trade names of amoxicillin, amoxil and timox [37–39].

The amoxicillin is a semi-synthetic drug, which belongs to a class of antibiotics called the penicillins (β-lactam antibiotics). This drug has been shown to be effective against a wide range of infections caused by gram-positive and gram-negative bacteria and is used for the treatment and prevention of respiratory, gastrointestinal, urinary and skin bacterial infections due to its pharmacological and pharmacokinetics properties [37, 40, 41]. Besides its use in human medicine, amoxicillin is also used for treating and preventing animal diseases as well as it is used as growth promoters for many domestic and food animals, including dogs, cats, pigeons, horses, broiler chickens, pigs, goats, sheep, pre-ruminating calves, cattle and fishes [42, 43]. It is well absorbed from gastrointestinal tract. The apparent volume of distribution of amoxicillin is approximately 0.26-0.31L/Kg and widely distributed to many tissues, including liver, lungs, prostate muscle, bile, ascetic, pleural and synovial fluids, and ocular fluids, accumulates in the amniotic fluid and crosses the placenta but penetrates poorly into the central nervous system unless inflammation is present. It is approximately 17–20% bound to human plasma proteins, primarily to albumin [44, 45].

Amoxicillin is very closely related to ampicillin with the same spectrum of activity and potency but is much better absorbed when given orally, achieving blood concentrations approximately twice as high as those obtained with ampicillin [37].

It acts binding to penicillin binding protein (PBP-1A) located inside the bacterial cell wall, the amoxicillin acylate the penicillin-sensitive transpeptidase C-terminal domain by opening the lactam ring causing inactivation of the enzyme, prevents the formation of a cross-link of two linear peptidoglycan strands, inhibiting the third and last stage of bacterial cell wall synthesis, which is necessary for cell division and cell shape and other essential processes, producing as a consequence the lisis of the bacteria cells [37, 46–49]. The two major metabolites of amoxicillin are amoxicilloic acid and piperazine-2, 5-dione (diketopiperazine). These metabolites have lost antibacterial activity of the parent component, but the amoxicilloic acid could have potential allergic properties [50–52].

The drug´s terminal half-life of elimination is 1 to 1.5 hours. Excretion of amoxicillin is predominantly renal, more than 80% of the original drug is recovered unchanged in the urine, leading to very high urinary concentrations and is also secreted in milk [53–55].
