Biliary and renal excretion, hepatic metabolism, and hepatic subcellular distribution of metronidazole in the rat

Nicholas F La Russo, Donald G. Lindmark, Miklós Müller

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Abstract

We studied the biliary and renal excretion, hepatic metabolism, and hepatic subcellular distribution of [14C]metronidazole in bile fistula rats. An average of 71.1 per cent of an intraduodenal or intravenous dose of [14C]metronidazole was excreted in 24 hr, 23.9 per cent in bile and 47.6 per cent in urine. Renal pedicle ligation caused a 150 per cent increase in biliary excretion of label, whereas phenobarbital pretreatment had no effect. The majority of label in bile and urine was associated with a polar derivative, tentatively identified by thin-layer chromatography and enzymatic hydrolysis as the monoglucuronide conjugate of metronidazole. After intraduodenal administration of purified conjugated [14C]metronidazole to rats with ligated renal pedicles, only a small amount of label (12.6 per cent of dose in 24 hr) appeared in bile. Growth inhibition studies showed the glucuronide conjugate to be devoid of antimicrobial activity against a metronidazole-sensitive organism, Tritrichomonas foetus. Uptake studies indicated that these organisms were incapable of concentrating conjugated metronidazole. Fractionation of rat liver homogenates by differential centrifugation after intravenous [14C]metronidazole showed that 90 per cent of label present in liver was in the non-particulate fraction. Our results in rats indicate that metronidazole undergoes an enterohepatic circulation and that the liver plays a major role in the metabolism and excretion of this compound.

Original languageEnglish (US)
Pages (from-to)2247-2254
Number of pages8
JournalBiochemical Pharmacology
Volume27
Issue number18
DOIs
StatePublished - 1978
Externally publishedYes

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Metronidazole
Metabolism
Rats
Liver
Bile
Labels
Tritrichomonas foetus
Urine
Enterohepatic Circulation
Kidney
Thin layer chromatography
Enzymatic hydrolysis
Centrifugation
Renal Elimination
Hepatobiliary Elimination
Glucuronides
Phenobarbital
Fractionation
Thin Layer Chromatography
Fistula

ASJC Scopus subject areas

  • Pharmacology

Cite this

Biliary and renal excretion, hepatic metabolism, and hepatic subcellular distribution of metronidazole in the rat. / La Russo, Nicholas F; Lindmark, Donald G.; Müller, Miklós.

In: Biochemical Pharmacology, Vol. 27, No. 18, 1978, p. 2247-2254.

Research output: Contribution to journalArticle

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