The Fate and Excretion of Polythiazide¹ in the Dog

Abstract

Polythiazide in the Dog 491 AG., Basle, and Burroughs Wellcome (Aust.) Ltd., for supplying lysergic acid diethylamide and ergometrine. The pharmacological testing of the LSD metabolites was carried out by Miss J. N. Pen-

Kinetics of polythiazide

“…N-Demethylation of poly thiazide has been shown not to occur in dogs. 16 Linearity was demonstrated by fortification of plasma with poly thiazide at concentrations of 0.2 to 5 ng/mI (Fig. 1).…”

“…Peak concentrations are seen at 5 hr in most of the subjects, with some later values; the delay in achieving peak levels may indicate some enterohepatic recirculation of drug, although studies in dogs indicate that the drug is primarily cleared via the kidneys. 16 Urinary excretion of poly thiazide is indicated in Table III. Creatinine determinations revealed that 5 of the subjects had levels below 60% of that expected, indicating incomplete collection of urine; poly thiazide concentrations for these subjects were not included in the means.…”

“…14 Sensitivities of 2 to 10 ILg/ml are achieved which are insufficient for the determination of poly thiazide after therapeutic doses, but used to determine lO-mg dose has recently been described 2 ; the levels in urine of dogs receiving 100 mg/kg. 16 sensitivity limit is approximately 5 ng/ml. A A gas chromatographic assay for benliquid chromatographic assay for hydrochlodrofiumethiazide adequate for the determination rothiazide in human serum with a sensitivity of of human plasma concentrations following a 50 ng/ml has been published.…”

“…This is similar to values of 29% and 32% in dogs receiving too mg/kg intravenously. 16 In man, the remainder is presumably cleared after metabolic changes as well as by elimination in the feces. Biliary secretion of chlorothiazide by the dog has been described.…”

High-Pressure Liquid Chromatographic Analysis of Polythiazide in Pharmaceutical Tablet Formulations

“…Methods for the determination of polythiazide include TLC (2), spectrophotometry (3)(4)(5), column chromatography (6), and polarography (7,s). However, these methods do not have the rapidity, simplicity, sensitivity, and accuracy of the high-pressure liquid chromatographic (HPLC) methodology.…”