Lung distribution of the chemopreventive agent difluoromethylornithine (DFMO) following oral and inhalation delivery

被引:14
作者
Liao, XM
Liang, W
Wiedmann, T
机构
[1] Univ Minnesota, Dept Pharmaceut, Minneapolis, MN 55455 USA
[2] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA
[3] Ohio State Univ, Sch Med, Div Hematol & Oncol, Columbus, OH USA
关键词
aerosol; chemoprevention; DFMO; lung cancer; pharrnacokinetics;
D O I
10.1080/01902140490517836
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
The inhalation delivery of difluoromethylornithine (DEMO) was evaluated to determine its feasibility for use in lung cancer chemoprevention. Aerosol droplets of DEMO were produced, and the solvent was removed by a reflux (trying column. Equivalent closes of DFMO (40 mg/kg) were given over 10 minutes by inhalation and by gavage, and the serum and tissue levels were determined. Inhalation, of DEMO resulted in, a peak lung concentration 80 times higher and area under the curve (AUC) that was 35 times higher than. oral dosing. The estimated pharmacokinetic advantage based on. serum. and lung AUCs was 13 in favor of inhalation.
引用
收藏
页码:755 / 769
页数:15
相关论文
共 17 条
[1]  
[Anonymous], 1988, ANN OCCUP HYG, DOI [DOI 10.1093/ANNHYG/32.INHALED_, DOI 10.1093/ANNHYG/32.INHALED_PARTICLES_VI.53]
[2]   HIGH-PRESSURE LIQUID-CHROMATOGRAPHIC ANALYSIS OF EFLORNITHINE IN SERUM [J].
COHEN, JL ;
KO, RJ ;
LO, ATL ;
SHIELDS, MD ;
GILMAN, TM .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1989, 78 (02) :114-116
[3]  
Dahl AR, 2000, CLIN CANCER RES, V6, P3015
[4]  
Fabian CJ, 2002, CLIN CANCER RES, V8, P3105
[5]   ASSAY OF ALPHA-DIFLUOROMETHYLORNITHINE IN BODY-FLUIDS AND TISSUES BY AUTOMATIC AMINO-ACID-ANALYSIS [J].
GROVE, J ;
FOZARD, JR ;
MAMONT, PS .
JOURNAL OF CHROMATOGRAPHY, 1981, 223 (02) :409-416
[6]   MEASUREMENT OF THE RESPIRATORY VOLUMES OF LABORATORY ANIMALS [J].
GUYTON, AC .
AMERICAN JOURNAL OF PHYSIOLOGY, 1947, 150 (01) :70-77
[7]   KINETICS OF ALPHA-DIFLUOROMETHYLORNITHINE - AN IRREVERSIBLE INHIBITOR OF ORNITHINE DECARBOXYLASE [J].
HAEGELE, KD ;
ALKEN, RG ;
GROVE, J ;
SCHECHTER, PJ ;
KOCHWESER, J .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1981, 30 (02) :210-217
[8]  
LOISEAU PM, 1995, J CHROMATOGR A, V716, P381
[9]   RANDOMIZED PHASE-I CHEMOPREVENTION DOSE-SEEKING STUDY OF ALPHA-DIFLUOROMETHYLORNITHINE [J].
LOVE, RR ;
CARBONE, PP ;
VERMA, AK ;
GILMORE, D ;
CAREY, P ;
TUTSCH, KD ;
POMPLUN, M ;
WILDING, G .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (09) :732-737
[10]  
Meyskens FL, 1999, CLIN CANCER RES, V5, P945