RT Journal Article
SR Electronic
T1 Metabolism and Disposition of the Antihypertensive Agent Moxonidine in Humans
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 334
OP 342
DO 10.1124/dmd.31.3.334
VO 31
IS 3
A1 Minxia M. He
A1 Trent L. Abraham
A1 Thomas J. Lindsay
A1 Hans C. Schaefer
A1 Isabelle J. Pouliquen
A1 Chris Payne
A1 Boris Czeskis
A1 Lisa A. Shipley
A1 Stuart D. Oliver
A1 Malcolm I. Mitchell
YR 2003
UL http://dmd.aspetjournals.org/content/31/3/334.abstract
AB The metabolism and pharmacokinetics of moxonidine, a potent central-acting antihypertensive agent, were studied in four healthy subjects after a single oral administration of approximately 1 mg (∼60 μCi) of [14C3]moxonidine. Moxonidine was rapidly absorbed, with peak plasma concentration achieved between 0.5 to 2 h postdose. The maximal plasma concentration and the area under the curve of unchanged moxonidine are lower than those determined for radioactivity, indicating presence of circulating metabolite(s). The total recovery of radiocarbon over 120 h ranged from 99.6 to 105.2%, with 92.3 to 103.3% of the radioactivity excreted in the urine and only 1.9 to 7.3% of the dose excreted in the feces. Thus, renal elimination represented the principal route of excretion of radioactivity. Metabolites of moxonidine were identified in urine and plasma samples by high performance liquid chromatography and liquid chromatography-tandem mass spectrometry. Oxidation of moxonidine on the methyl group or on the imidazoline ring resulted in the formation of hydroxymethyl moxonidine, hydroxy moxonidine, dihydroxy moxonidine, and dehydrogenated moxonidine. Metabolite profiling results indicated that parent moxonidine was the most abundant component in the urine. The dehydrogenated moxonidine was the major urinary metabolite as well as the major circulating metabolite. Moxonidine also underwent phase II metabolism, generating a cysteine conjugate. In summary, moxonidine is well absorbed after oral administration. The major clearance pathway for moxonidine in humans is via renal elimination. Furthermore, seven metabolites were identified with three metabolites unique to humans. The American Society for Pharmacology and Experimental Therapeutics