The use of pig hepatocytes to study the nature of protein-bound metabolites of furazolidone: a new analytical method for their detection.
The biotransformation of furazolidone, both in vivo and in vitro, results in the formation of so-called bound metabolites. Following the incubation of pig hepatocytes with [14C]furazolidone, a dose- and time-related increase in the formation of bound metabolites was observed. After withdrawal of the drug from the medium, levels decreased gradually to about 50% within 36 hr. Using a newly developed method, it was shown that in the case of cells and liver microsomes at least 70% of the bound residues still contained the 3-amino-2-oxazolidinone (AOZ) side chain of furazolidone. For liver samples of piglets that had been treated orally with the drug for 10 days, followed by withdrawal periods of 2 hr or 14 days, fractions of releasable AOZ were 23 and 14%, respectively, equivalent to levels of 3.8 and 0.3 micrograms furazolidone/g of tissue, respectively. The release of the AOZ side chain of furazolidone from at least part of the bound metabolites shows their drug-related nature and highlights the requirement for both adequate withdrawal periods and the need for appropriate control methods. The relative simplicity of the newly developed method may be helpful in further establishing and controlling adequate withdrawal periods.
Hoogenboom
L A
LA
State Institute for Quality Control of Agricultural Products (RIKILT), Wageningen, The Netherlands.
van Kammen
M
M
Berghmans
M C
MC
Koeman
J H
JH
Kuiper
H A
HA
D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005664:Furazolidone / Q000378:metabolism / Q000493:pharmacokinetics*; D008862:Microsomes, Liver / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000032:analysis / Q000378:metabolism; D010080:Oxazoles / Q000032:analysis / Q000378:metabolism; D023303:Oxazolidinones; D013552:Swine
D008996:Monoamine Oxidase Inhibitors; D010080:Oxazoles; D023303:Oxazolidinones; D005664:Furazolidone; C000209:3-amino-2-oxazolidinone