Tissue Distribution and Excretion of Amodiaquine in the Rat

Abstract

— ¹⁴C‐Labelled amodiaquine ([¹⁴C]AQ) has been administered to male Wistar rats by oral and intravenous routes (n = 6 for each route of administration). Excretion of total ^14C‐activity was predominantly in the faeces after both oral and intravenous administration. After oral administration 86 ± 8.3% (mean ± s.d.) of the ¹⁴C administered had been excreted (77 ±9% in the faeces, 7 ± 1 % in the urine and 2 ± 2% in cage washings) over 72 h. Of the ¹⁴C administered, 4 ± 1% was recovered from the tissues, and this was widely distributed, with the main organs of accumulation being kidney, liver, red bone marrow and spleen. After intravenous administration, 102.6 ± 9.7% of the ¹⁴C had been excreted (90.9 ± 9.6% in faeces, 10.9 ± 0.8% in urine and 0.5 ± 0.2% in cage washings) over 72 h. High‐performance liquid chromatographic analysis of urine and faeces samples following oral administration of ¹⁴C‐AQ (8.6 mg kg⁻¹; base) revealed recoveries of 210 ± 70 μg amodiaquine (AQ) and 123 ± 32 μg desethylamodiaquine (AQm) in the faeces, and 2.4 ± 0.5 μg AQ and 18.5 ± 4.1 μg AQm in the urine. Female Wistar rats (n = 6) each received [¹⁴C]AQ orally and were killed at the following times: 0.5, 1, 3, 6, 24 and 48 h. Autoradiographs were prepared from each animal and these revealed significant amounts of radioactivity in the tissues at 48 h. This was accumulated maximally by liver and kidney. Radioactivity was detected in bone marrow at 48 h. These data show that after oral administration of [¹⁴C]AQ to rats, significant amounts of radiolabel were accumulated in the liver, and haemopoietic tissues, which are the sites of observed toxicity in man. Of the excreted radiolabel, only a small proportion was in the form of AQ or AQm.