Oryzalin [3,5-dinitro-N,N-di(n-propyl)benzensulfanilamide] is a widely used
sulfonamide herbicide that selectively inhibits microtubule formation in algae and higher plants.
Oryzalin has also been found to be an inhibitor of intracellular free Ca2+ signaling in mammalian cells and to have antitumor activity in animals. Despite its widespread use there have been no reports of the pharmacokinetics of
oryzalin in animals or man. A reversed-phase high-performance liquid chromatographic (HPLC) method was developed to measure
oryzalin in
biological fluids. Following repeated daily administration of
oryzalin to mice by the i.p. route at 200 mg/kg, or the p.o. route at 300 mg/kg, peak plasma concentrations of up to 25 micrograms/ml were achieved. The half life for
oryzalin in plasma of mice given i.p.
oryzalin was 14.3 h with a clearance of 0.07 l/h. A major metabolite of
oryzalin, N-depropyloryzalin, was identified in plasma and its structure confirmed by mass spectral analysis (M+H+ = 305). This metabolite was cleared more rapidly than
oryzalin with a half life of 1.15 h and a clearance of 0.17 l/h. N-Depropyloryzalin caused similar inhibition of colony formation by HT-29
colon cancer cells as
oryzalin with IC50 = 8 micrograms/ml. The results suggest that
oryzalin and its N-depropyl metabolite can inhibit
tumor colony formation at pharmacologically achievable levels.