Metabolism of penicillins to penicilloic acids and 6-aminopenicillanic acid in man and its significance in assessing penicillin absorption.
Penicillins can be metabolized to penicilloic acids in man, the extent being dependent on the penicillin structure. In the phenoxy penicillin series, phenoxymethyl penicillin was found to be particularly unstable, but the higher homologues were more stable. In the isoxazolyl series, oxacillin was unstable, and progressive insertion of halogen in the phenyl ring increased stability. Ampicillin and amoxycillin showed some instability, ampicillin possibly being the more stable. After intramuscular administration, carbenicillin was very stable in the body, ampicillin was fairly stable, and benzyl penicillin was unstable. It is important to take into account the penicilloic acid content of urine when estimating total absorption of a penicillin. Increased stability in the body as well as slower renal clearance can lead to high concentrations in the serum. Penicilloic acids seemed to be more slowly cleared from the body than penicillins. The liver is probably the site of inactivation.
D000042:Absorption; D000328:Adult; D000588:Amines / Q000096:biosynthesis; D000596:Amino Acids / Q000096:biosynthesis; D001681:Biological Assay; D002264:Carboxylic Acids / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D010397:Penicillanic Acid / Q000096:biosynthesis* / Q000378:metabolism / Q000031:analogs & derivatives; D010406:Penicillins / Q000008:administration & dosage / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000096:biosynthesis*
D000588:Amines; D000596:Amino Acids; D002264:Carboxylic Acids; D010406:Penicillins; D013844:Thiazoles; C008782:penicilloic acid; D010397:Penicillanic Acid