Absorption and disposition characteristics of nitrofurantoin in dogs.

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Niazi S, Vishnupad KS, Veng-Pedersen P

Absorption and disposition characteristics of nitrofurantoin in dogs.

Biopharm Drug Dispos. 1983 Jul-Sep;4(3):213-23.

PubMed ID
6626697 [ View in PubMed
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Abstract

This study reports the disposition kinetic properties of nitrofurantoin in dogs following single intravenous and oral administration of various formulations of nitrofurantoin. Also reported here is the effect of delaying gastric emptying by food and atropine on the absorption characteristics of nitrofurantoin. The drug absorption parameters calculated using a deconvolution computer program indicate that the rate and extent of enterohepatic recycling affects the elimination and absorption rate constants and thus confound the bioavailability calculations of nitrofurantoin, heretofore unrecognized in the literature. The plasma half-life following intravenous administration was 31 min (monoexponential equation) with little effect of enterohepatic recycling noted. Following oral administration, a biexponential equation with lag-time was used to fit the blood levels. The absorption half-lives were higher when nitrofurantoin was administered as a solid dosage form compared to a solution. The absorption half-lives following tablet administration ranged from 30 to 72 min and were not affected by food or atropine. The elimination half-lives following oral administration ranged from 19 to 87 min with significantly prolonged elimination when solid dosage forms were administered compared to solution. The extent of absorption ranged from 38 to 120 per cent. A direct correlation between the absorption and elimination half-life was established, indicating that increased biliary recycling direct affects the apparent disposition half-life. The three brands of nitrofurantoin tested for bioavailability showed that the use of blood levels without appropriate corrections for biliary recycling are not suitable for bioavailability testing of nitrofurantoin. The use of urinary excretion data in evaluating nitrofurantoin bioavailability is also questioned in the study.

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