Plasma and skin blister fluid concentrations of metronidazole and its hydroxy metabolite after oral administration.
Plasma and cantharidin-induced skin blister fluid concentrations of metronidazole and its main metabolite-hydroxymetronidazole were determined after a single and multiple oral doses. Metronidazole is nitroimidazole compound applied for the treatment of Protozoa infections. It is also active against anaerobic bacteria. The maximum concentrations of unchanged drug and its metabolite following a single oral dose of 2 g were observed after 1 +/- 1 and 11 +/- 2 h in plasma, whereas in blister fluid after 6 +/- 2 and 16 +/- 5 h, respectively. The average ratio of area under concentration time curve (AUC) in blister fluid to that of plasma was 1.02 +/- 0.12 for parent drug and 1.02 +/- 0.02 for the metabolite. After multiple doses of metronidazole (0.25 g every 8 h) the concentrations of unchanged drug in plasma and blister fluid, collected before the morning dose and 2 h after its administration, exceeded the minimal inhibitory concentrations for majority of susceptible pathogens. Hydroxymetronidazole concentrations in body fluids at steady-state amounted to about 30-50% of the parent drug and they could contribute to the overall activity against susceptible microorganisms since antibacterial activity of the metabolite is about 30-65% that of the metronidazole.
Klimowicz
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Department of Dermatology and Venereology, Pomeranian Medical Academy, Szczecin, Poland.
Nowak
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Bielecka-Grzela
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S
D000284:Administration, Oral; D000328:Adult; D001768:Blister / Q000139:chemically induced / Q000378:metabolism*; D002193:Cantharidin; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged
D008795:Metronidazole; D002193:Cantharidin