Pharmacokinetics and metabolism of indapamide: A review

SummaryThe comparative pharmacokinetics and metabolism of indapamide have been studied in the dog, rat and human using 14C-indapamide. The results indicate that the dog is kinetically more similar to man than to the rat, but all three species share common metabolic pathways. Indapamide is rapidly and completely absorbed within 1 hour in humans, reaching peak concentrations of 140 ng/ml after a 10 mg oral dose. Elimination from plasma is biphasic with an initial rapid elimination followed by a long terminal phase of 18 hours. Repeated administration does not alter the kinetics of the drug and maximal concentrations are measured within 3 days of dosing. Indapamide is comparatively lipid soluble and unlike more polar compounds of similar structure it is extensively metabolized to 19 metabolites, and less than 5 % is found unchanged in urine. The drug binds both to plasma protein (79 %) and carbonic anhydrase (98%) and over 40% of the dose is found in blood after 1 hour. Indapamide is also taken up by the vascular wall. It is this highly localized distribution, in contrast to compounds which concentrate in urine, which may account for the observed differences in the pharmacological and clinical activity of the drug.