Pharmacokinetics and Metabolism of Lonidamine in Rats: Evidence of Enterohepatic Recycling

Lonidamine (AF 1890), or diclondazolic acid: 1-[(2,4-dichlorophenyl) methyl]-1H-indazole-3-carboxylic acid, has been found to have antispermatogenic, embryotoxic, and interesting anticancer activities. This drug was demonstrated more active than AF1312/TS and tolnidamine, two closely related analogs...

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Bibliographic Details
Published in:Drug metabolism reviews 1997-01, Vol.29 (1-2), p.219-234
Main Authors: Besner, Jean-Guy, Leclaire, Robert, Roy, Julie J.
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Antineoplastic agents
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - metabolism
Antineoplastic Agents - pharmacokinetics
Area Under Curve
Bile - metabolism
Biological and medical sciences
Enterohepatic Circulation - physiology
General aspects
Half-Life
Indazoles - administration & dosage
Indazoles - metabolism
Indazoles - pharmacokinetics
Injections, Intravenous
Intestinal Absorption
Liver - metabolism
Male
Medical sciences
Models, Biological
Pharmacology. Drug treatments
Rats
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Summary:Lonidamine (AF 1890), or diclondazolic acid: 1-[(2,4-dichlorophenyl) methyl]-1H-indazole-3-carboxylic acid, has been found to have antispermatogenic, embryotoxic, and interesting anticancer activities. This drug was demonstrated more active than AF1312/TS and tolnidamine, two closely related analogs. The preliminary pharmacokinetics of lonidamine (LND) have been described in rats, rabbits and monkeys by Segre and Catanese. The data reported indicate that plasma concentrations after oral administration in rabbits, oral and intravenous administration in rats, and oral administration in monkeys can be predicted with a bicompartmental open model. The biological half-life varies according to species; mean values are: 7 h for rabbits, 14 h for rats, and 9 h for monkeys. In this preliminary screening study, it was reported that unchanged LND was poorly excreted in urine and bile of rat. Furthermore, in monkey, pharmacokinetic was apparently dose dependent for oral doses between 10 and 500 mg/kg.
ISSN:0360-2532
1097-9883
DOI:10.3109/03602539709037583