Pharmacokinetic studies of the herbicide and antitumor compound oryzalin in mice

被引:8
作者
Dvorakova, K [1 ]
Dorr, RT [1 ]
Gallegos, A [1 ]
McClure, T [1 ]
Powis, G [1 ]
机构
[1] UNIV ARIZONA,HLTH SCI CTR,ARIZONA CANC CTR,TUCSON,AZ 85724
来源
JOURNAL OF CHROMATOGRAPHY B | 1997年 / 696卷 / 02期
关键词
oryzalin;
D O I
10.1016/S0378-4347(97)00261-2
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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 mu g/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 mu g/ml. The results suggest that oryzalin and its N-depropyl metabolite can inhibit tumor colony formation at pharmacologically achievable levels. (C) 1997 Elsevier Science B.V.
引用
收藏
页码:275 / 281
页数:7
相关论文
共 8 条
[1]   MEASUREMENT OF HUMAN-TUMOR CELL-GROWTH IN SOFT-AGAR CULTURES USING COMPUTER-ASSISTED VOLUME ANALYSIS [J].
ALLEY, MC ;
LIEBER, MM .
BRITISH JOURNAL OF CANCER, 1985, 52 (02) :205-214
[2]   DRUGS WITH COLCHICINE-LIKE EFFECTS THAT SPECIFICALLY DISASSEMBLE PLANT BUT NOT ANIMAL MICROTUBULES [J].
BAJER, AS ;
MOLEBAJER, J .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1986, 466 :767-784
[3]  
DECKER OD, 1976, ANAL METHODS PESTIC, V8, P433
[4]  
KENNEDY JH, 1977, J CHROMATOGR SCI, V15, P70
[5]   ORYZALIN, A DINITROANILINE HERBICIDE, BINDS TO PLANT TUBULIN AND INHIBITS MICROTUBULE POLYMERIZATION INVITRO [J].
MOREJOHN, LC ;
BUREAU, TE ;
MOLEBAJER, J ;
BAJER, AS ;
FOSKET, DE .
PLANTA, 1987, 172 (02) :252-264
[6]  
POWIS G, 1997, IN PRESS CANC CHEMOT
[7]  
Royer I, 1996, CANCER RES, V56, P58
[8]   THE BIOCHEMICAL-MECHANISM OF ACTION OF THE DINITROANILINE HERBICIDE ORYZALIN [J].
STRACHAN, SD ;
HESS, FD .
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY, 1983, 20 (02) :141-150