DEVELOPMENT OF AN INTRAVENOUS DESFERRIOXAMINE MESYLATE TREATMENT PROTOCOL FOR SWINE - MONITORING OF DESFERRIOXAMINE AND METABOLITES BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

被引:4
作者
FISHER, EA
MCLACHLAN, DR
KRUCK, TPA
MUSTARD, RA
机构
[1] UNIV TORONTO,DEPT PHYSIOL,ROOM 3318,MED SCI BLDG,TORONTO M5S 1A8,ONTARIO,CANADA
[2] UNIV TORONTO,DEPT MED,TORONTO M5S 1A8,ONTARIO,CANADA
[3] UNIV TORONTO,DEPT SURG,TORONTO M5S 1A8,ONTARIO,CANADA
关键词
desferrioxamine; high-performance liquid chromatography; metabolites; swine model;
D O I
10.1159/000138730
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Desferrioxamine (DFO) metabolism and its pharmacokinetics were studied in a swine model using high-performance liquid chromatography. DFO and three iron-binding metabolites occurred in plasma. Interindividual differences in pharmacokinetics and metabolism were observed. Urine analysis in 4 pigs showed three iron-binding metabolites. The mean percent dose excreted in urine in the form of the parent drug was 45 ± 10% and 10 ± 2% (means ± SD) in the form of metabolites. Of the total amount of the parent drug infused, 3 h after initiation, 87% was in the form of DFO, whereas 13% was present as the DFO-iron III complex which represented 45 mg of urinary iron elimination. The described DFO infusion protocol provides for sufficient DFO to chelate signficant amounts of ferric iron in excess of normal levels, thus allowing experimental studies of iron chelation in a variety of disease states.
引用
收藏
页码:263 / 271
页数:9
相关论文
共 22 条
  • [1] PHARMACOKINETICS AND RENAL ELIMINATION OF DESFERRIOXAMINE AND FERRIOXAMINE IN HEALTHY-SUBJECTS AND PATIENTS WITH HEMOCHROMATOSIS
    ALLAIN, P
    MAURAS, Y
    CHALEIL, D
    SIMON, P
    ANG, KS
    CAM, G
    LEMIGNON, L
    SIMON, M
    [J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1987, 24 (02) : 207 - 212
  • [2] DEFEROXAMINE INCREASES SKIN FLAP SURVIVAL - ADDITIONAL EVIDENCE OF FREE-RADICAL INVOLVEMENT IN ISCHEMIC FLAP SURGERY
    ANGEL, MF
    NARAYANAN, K
    SWARTZ, WM
    RAMASASTRY, SS
    KUHNS, DB
    BASFORD, RE
    FUTRELL, JW
    [J]. BRITISH JOURNAL OF PLASTIC SURGERY, 1986, 39 (04): : 469 - 472
  • [3] ASHBAUGH DG, 1967, LANCET, V2, P319
  • [4] ASKOY M, 1984, HYPERTENSION IRON CH, P11
  • [5] BLAKE DR, 1985, Q J MED, V56, P345
  • [6] THE IRON CHELATOR DESFERRIOXAMINE ATTENUATES POSTISCHEMIC VENTRICULAR DYSFUNCTION
    BOLLI, R
    PATEL, BS
    ZHU, WX
    ONEILL, PG
    HARTLEY, CJ
    CHARLAT, ML
    ROBERTS, R
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1987, 253 (06): : H1372 - H1380
  • [7] EFFECT OF AN IRON-CHELATING AGENT ON LYMPHOCYTE-PROLIFERATION
    BOWERN, N
    RAMSHAW, IA
    BADENOCHJONES, P
    DOHERTY, PC
    [J]. AUSTRALIAN JOURNAL OF EXPERIMENTAL BIOLOGY AND MEDICAL SCIENCE, 1984, 62 (DEC): : 743 - 754
  • [8] FOA P, 1986, SCAND J HAEMATOL, V36, P107
  • [9] FRY DE, 1980, ARCH SURG-CHICAGO, V115, P136
  • [10] FUDMAN EJ, 1987, J RHEUMATOL, V14, P686