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  • Title: Excretion of nitrofurantoin in dog hepatic bile.
    Author: Conklin JD, Wagner DL.
    Journal: Br J Pharmacol; 1971 Sep; 43(1):140-50. PubMed ID: 5136454.
    Abstract:
    1. After the intravenous administration of nitrofurantoin sodium to dogs at nitrofurantoin doses of 1.5-24.0 mg/kg, a substantial amount of nitrofurantoin is excreted in bile. The bile to blood drug ratios were about 200. A marked hydrocholeretic effect which correlated directly with the amount of nitrofurantoin administered was also observed.2. The excretion of nitrofurantoin in bile and the hydrocholeretic effect were linear with the dose of drug over the range 1.5-12.0 mg/kg. Maximum increases in hepatic bile flows were usually from 5-10 ml/0.5 h, while average control bile flow was 1.6 ml +/- S.D. 0.6/0.5 hours. The lowest dose at which the hydrocholeretic effect was still detectable was 0.09 mg/kg.3. Apparent saturation of the biliary excretion system for nitrofurantoin and the hydrocholeretic mechanism occurred after a dose of 24.0 mg/kg. Saturation of the urinary system for nitrofurantoin excretion was noted after a dose of 6.0 mg/kg.4. Biliary nitrofurantoin recoveries ranged from 16.5% +/- S.D. 4.2 to 22.6% +/- S.D. 4.7 for the 6 h period after doses of 1.5, 3.0, and 6.0 mg/kg. Urinary nitrofurantoin recoveries for the same interval ranged from 24.1% +/- S.D. 6.6 to 36.2% +/- S.D. 8.3.5. In comparison to values obtained in normal dogs, only about one-tenth of the drug excretion in bile and about one-fifth of the hydrocholeretic effect were obtained after intravenous drug administration to dogs with hepatic impairment induced by CCl(4).
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