Effect of penicillin-based antibiotics, amoxicillin, ampicillin, and piperacillin, on drug-metabolizing activities of human hepatic cytochromes P450.

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Niwa T, Morimoto M, Hirai T, Hata T, Hayashi M, Imagawa Y

Effect of penicillin-based antibiotics, amoxicillin, ampicillin, and piperacillin, on drug-metabolizing activities of human hepatic cytochromes P450.

J Toxicol Sci. 2016 Feb;41(1):143-6. doi: 10.2131/jts.41.143.

PubMed ID

26763401 [ View in PubMed

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Abstract

The effects of three kinds of penicillin-based antibiotics, amoxicillin, ampicillin, and piperacillin, on drug-metabolizing activity of human hepatic cytochrome P450 (P450 or CYP) were investigated. Metabolic activities of P450s expressed in recombinant Escherichia coli at substrate concentrations around the Michaelis constant were compared in the presence or absence of the antibiotics. Amoxicillin, ampicillin, and piperacillin at 0.5 or 1 mM concentrations neither inhibited nor stimulated CYP2C9-mediated tolbutamide methylhydroxylation, CYP2D6-mediated dopamine formation from p-tyramine, or CYP3A4- or CYP3A5-mediated testosterone 6beta-hydroxylation. However, amoxicillin and piperacillin inhibited CYP2C8-mediated aminopyrine N-demethylation at 50% inhibitory concentration of 0.83 and 1.14 mM, respectively. These results suggest that piperacillin might inhibit CYP2C8 clinically, although the interactions between these three penicillin-based antibiotics and other drugs that are metabolized by P450s investigated would not be clinically significant.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Amoxicillin	Cytochrome P450 2C8	Protein	Humans	Unknown	Inhibitor	Details