Metabolism of 125Iodochloroxyquinoline in Man

Abstract

SummaryThe absorption and excretion of 125I-labelled iodochloroxyquinoline (Vio-form®, CIBA) was studied in 3 euthyroid and 3 hyperthyroid subjects. The tracer doses of 0.1—1.0mg/kg or 7.6—60mg, and corresponding to 38.5—68 μCi, were given orally.The average absorption amounted to 43.6 per cent as judged from the urinary excretion during the period of study (10—18 days). The absorption was very rapid, the highest plasma concentration values (0.63—6.5 per cent of the dose/1) being invariably found in the first plasma sample drawn 4 hrs after administration. In two cases the faecal excretion was measured. It amounted to 33 and 64 per cent, the total urinary und faecal recovery in these cases being about 95 per cent in 6—9 days. The thyroid uptake was very low, about 0.4 per cent, and corresponded to 0.11 mg of iodine.The plasma disappearance curves consisted of two or more components. The initial rapid phase had a T1/2 of about 0.3 days and the last phase a T1/2 of 11 days, on the average. The urinary excretion curve showed an initial phase corresponding to a single exponential function and lasted for several days after which the curve attained a more horizontal direction. In two euthyroid subjects there was a spontaneous increase in the urinary excretion, starting on the days 7 and 11 and lasting for several days. This coincided with an increase in the absolute dialysable plasma radioactivity.There was also a constant increase in the dialysable fraction during the experiment. This was thought to indicate a relative increase in one or several highly water-soluble metabolites. The use of TCA-precipitation for studying the protein-bound portion gave higher values for the nonprotein-bound portion in the beginning of the experiment. This was probably due to splitting from the plasma proteins of some loosely bound metabolites. At the end of the experiment both methods gave more equal values for the nonprotein-bound fraction.The renal clearance for the plasma dialysable fraction above a concentration of 15—23 ng/ml was that of a substance actively secreted by the tubules. The maximal renal clearance calculated from the total plasma concentration averaged 12 ml/min.Attempts were made to study the effect of hyperthyroidism and thyroid blocking agents on the distribution of 125ICOQ. In hyperthyroid cases the initial disposal rate appeared to be faster than in the euthyroid cases. In the later phase, however, the plasma curve and the urinary excretion remained on a higher level. The result of thyroid blocking agents was inconclusive.

Metabolism of mono- and dichlorohydroxyquinolines-Cl36 in the rat and calf

“…38 to 50% ICOQ was found in the urine of rabbits receiving oral doses of 20 mg/kg/day for 7 days (Haskins and Luttermoser, 1953). A man receiving a single dose of 0.1 to 1 mg of ICOQ excretes 43% in his urine as glucuronide and sulfate conjugates within 10 to 18 days (Liewendahl and Lamberg, 1967). This confirms other experiments (Ritter and Jermann, 1966).…”

Current biomarkers and treatment strategies in Alzheimer disease: An overview and future perspectives

“…CQ had been utilised as a therapy in cattle and humans with Zn-deficiency disorders ( Kilic et al, 2012 ); ( Fiehn, 2016 ).CQ is extremely lipophilic, rapidly absorbed, and capable of gluconation and sulfation. It can also penetrate the BBB and be excreted in the urine and faeces ( Woo et al, 2011 ), ( Liewendahl and Lamberg, 1967 ); ( Zuccato and Cattaneo, 2009 ); ( Gaggelli et al, 2006 ).…”