Ej. Eisenberg et al., ISOLATION AND IDENTIFICATION OF A METABOLITE OF CIDOFOVIR FROM RAT-KIDNEY, Journal of pharmaceutical and biomedical analysis, 16(8), 1998, pp. 1349-1356
Cidofovir is an acyclic nucleotide analog with potent and broad-spectr
um antiviral activity against adenoviruses and herpesviruses including
cytomegalovirus (CMV). Cidofovir undergoes intracellular phosphorylat
ion by host enzymes to cidofovir phosphate and cidofovir diphosphate (
the active form). An unidentified metabolite has been observed previou
sly in rat tissues and in urine of rabbits, rats and monkeys dosed wit
h cidofovir. In the present study this metabolite was isolated from ra
t kidney following an intravenous dose of 100 mg kg(-1) cidofovir. The
metabolite (metabolite I) was separated from cidofovir and impurities
using extraction on anion-exchange resin followed by preparative norm
al and reversed-phase high-performance liquid chromatography (HPLC). T
he isolated metabolite I was subjected to proton, C-13 and phosphorus
nuclear magnetic resonance (NMR and matrix-assisted laser desorption/i
onization mass spectroscopy, and confirmed to be cidofovir-phosphochol
ine. The uptake of cidofovir by rat kidney was saturated at an intrave
nous dose of 100 mg kg(-1), probably as a result of saturation of the
renal tubular secretion pathway. However, the relative abundance of ci
dofovir phosphocholine was not affected by dose. (C) 1998 Elsevier Sci
ence B.V. All rights reserved.