Amoxicillin isomers

A new metabolite detected in human urine by HPLC was identified as amoxicillin penamaldic acid, XI, on the basis of spectroscopic investigations of material, obtained by in vitro treatment of amoxicillin penicilloic acid, which was shown to co-ehite with the metabolite on HPLC [ISO], More detailed UV and NMR studies on material prepared in the same way showed that the assignment of XI was incorrect and that the new metabolite was the 5S diastereoisomer of the penicilloic acid, V, produced by epimerisation of the 5R isomer formed by hydrolysis of amoxicillin [43]. The presence of both isomers in rat and human urine has recently been confirmed by high field proton NMR [151]. 

Amoxicillin is well absorbed when given orally, with a bioavailability that appears to be much higher than expected in the light of its physico-chemical properties and the pH partition theory [191], Numerous studies show recovery of intact amoxicillin in urine after oral administration in the range 43 to 80 % after 6 to 8 hours, with most figures in the upper part of this range [147,171,172,187,188,190]. An additional 10 to 25 % of the dose appears in urine as the penicilloic acid [147,148,152,171,172,187] with a ratio of about 2 to 1 of the 5R to 5S isomers [152,171,172]. Amoxicillin is extensively distributed in body tissues and fluids, with adequate levels for antibacterial activity in most of them [187,188,190], The half life in serum is about one hour and is the same for oral, intramuscular and intravenous administration [187,188,190]. Co-administration with potassium clavulanate does not affect the absorption, distribution and excretion of amoxicillin [190]. 

R = />-CH3C6H5N, ( -isomer, has also been reported to inhibit type I Cephases. The 6-P-[bistrifluoromethane sulfonyl] amidopenicillanic acid [82954-44-7] (31, R = (CF3S02)2N), R/ = H, R" = R/// = CH3) was speculated to inhibit the penase from B. cereus by triflation or generation of an imine that reacts further with the enzyme. Several C-6 substituted amino penams have been reported to inhibit type I Cephases the complex hydroxyalkyl penicfllanic acid derivatives are reported to be potent P-lactamase inhibitors and synergists. In combination with amoxicillin, compound (31, R =... 

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