Spectrum, absorbtion, chemistry, and stability of amoxicillin

Spectrum, absorbtion, chemistry, and stability of amoxicillin
Spectrum
Based on its spectrum of activity, amoxicillin is classified as an aminopenicillin. amoxicillin are active in vitro against most gram-positive and gram-negative aerobic cocci (except penicillinase-producing strains), some gram-positive aerobic and anaerobic bacilli, and some spirochetes. The drugs are also active in vitro against some gram-negative aerobic and anaerobic bacilli. amoxicillin are inactive against Mycoplasma, Rickettsia, fungi, and viruses.
Amoxicillin generally has the same spectrum of activity and the same level of activity against susceptible organisms as ampicillin; however, amoxicillin is more active in vitro on a weight basis than ampicillin against enterococci and Salmonella but less active than ampicillin against Shigella and Enterobacter.

Absorption
Amoxicillin is generally stable in the presence of acidic gastric secretions, and 74-92% of a single oral dose of the drug is absorbed from the GI tract. Amoxicillin is more completely absorbed from the GI tract than is ampicillin, and peak serum concentrations of amoxicillin are generally 2-2.5 times higher than those attained with an equivalent oral dose of ampicillin. As oral dosage of amoxicillin is increased, the fraction of the dose absorbed from the GI tract decreases only slightly and peak serum concentrations and areas under the serum concentration-time curves (AUCs) increase linearly with increasing dosage.

Peak serum concentrations are usually reached 1-2 hours after oral administration of amoxicillin capsules, film-coated tablets, chewable tablets, or oral suspension in fasting and nonfasting adults. Following oral administration of a single 250- or 500-mg dose of amoxicillin, peak serum concentrations range from 3.5-5 or 5.5-11 mcg/mL, respectively. In one study in healthy, fasting adults who received a single 500-mg oral dose of amoxicillin, serum concentrations of the drug averaged 3.3, 6.7, 9.3, 5.8, and 0.6 mcg/mL at 30 minutes, 1 hour, 2 hours, 3 hours, and 4 hours, respectively, after the dose. The manufacturer states that serum concentrations attained following administration of 125- or 250-mg chewable tablets are similar to those attained when the same dose is given as the oral suspension containing 125 or 250 mg of the drug per 5 mL. In healthy adults who received a single 400-mg dose of amoxicillin given as a 400-mg chewable tablet or the oral suspension containing 400 mg of the drug per 5 mL (dose given at the start of a light meal), peak serum concentrations were attained approximately 1 hour after the dose and averaged 5.18 or 5.92 mcg/mL, respectively, and AUC averaged 17.9 or 17.1 mcg•hr/mL, respectively.

In one study in children 4-45 months of age receiving amoxicillin oral suspension in a dosage of 15 mg/kg daily, serum amoxicillin concentrations ranged from 2.4-8.5, 1.9-11.3, 1.7-6.4, 0.17-1.9, and 0.14-3.3 mcg/mL at 30 minutes, 1 hour, 2 hours, 4 hours, and 6 hours, respectively, after a dose.

Although presence of food in the GI tract reportedly results in lower and delayed peak serum concentrations of amoxicillin, the total amount of drug absorbed does not appear to be affected.

Chemistry
Amoxicillin is an aminopenicillin which differs structurally from ampicillin only in the addition of an hydroxyl group on the phenyl ring.

Amoxicillin is commercially available as the trihydrate. Potency of amoxicillin trihydrate is calculated on the anhydrous basis. Amoxicillin occurs as a white, practically odorless, crystalline powder and is sparingly soluble in water. When reconstituted as directed, amoxicillin oral suspensions have a pH of 5-7.5.

Amoxicillin is commercially available for oral administration as capsules, film-coated tablets, chewable tablets, or powder for oral suspension. Amoxicillin also is commercially available for oral administration in fixed-ratio combinations with clavulanate potassium.

Each 125-, 200-, 250-, or 400-mg amoxicillin chewable tablet contains 0.0019 mEq (0.044 mg), 0.0005 mEq (0.0107 mg), 0.0037 mEq (0.085 mg), or 0.0009 mEq (0.0215 mg) of sodium, respectively. The 200- and 400-mg chewable tablets contain aspartame which is metabolized in the GI tract to provide 1.82 or 3.64 mg of phenylalanine, respectively, following oral administration.

Stability
Amoxicillin capsules, 125- and 250-mg chewable tablets, and powder for oral suspension should be stored in tight containers at 20C or lower; amoxicillin 200- and 400-mg chewable tablets and amoxicillin film-coated tablets should be stored in tight containers at 25C or lower.

Following reconstitution, amoxicillin oral suspensions should preferably be refrigerated at 2-8C, but refrigeration is not necessary and the suspensions are stable for 14 days at room temperature or 2-8C.