TY - JOUR
T1 - Biliary and renal excretion, hepatic metabolism, and hepatic subcellular distribution of metronidazole in the rat
AU - Larusso, Nicholas F.
AU - Lindmark, Donald G.
AU - Müller, Miklós
PY - 1978
Y1 - 1978
N2 - 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.
AB - 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.
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U2 - 10.1016/0006-2952(78)90084-9
DO - 10.1016/0006-2952(78)90084-9
M3 - Article
C2 - 728175
AN - SCOPUS:0018141005
SN - 0006-2952
VL - 27
SP - 2247
EP - 2254
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 18
ER -