CLINICAL PHARMACOKINETICS OF IFOSFAMIDE IN COMBINATION WITH N-ACETYLCYSTEINE

被引:6
作者
BENVENUTO, JA [1 ]
AYELE, W [1 ]
LEGHA, SS [1 ]
RABER, MN [1 ]
NICAISE, C [1 ]
NEWMAN, RA [1 ]
机构
[1] BRISTOL MYERS SQUIBB CO,WALLINGFORD,CT 06492
关键词
IFOSFAMIDE; N-ACETYLCYSTEINE; PHARMACOKINETICS;
D O I
10.1097/00001813-199202000-00004
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The pharmacokinetics of ifosfamide were studied in 20 patients with soft tissue and bone sarcomas. Drug was administered as a 30-60 min i.v. infusion at 1.2 or 2.0 mg/m2/day for five consecutive days. Some patients also received 1.5 g/m2 of N-acetylcysteine (NAC) administered 3 times per day during the course of therapy. NAC had no effect on ifosfamide pharmacokinetics. There were significant differences in plasma half-life, area under the concentration-time curve and plasma clearance on day 1 versus day 5 of ifosfamide administration. Myelosuppression and granulocytopenia correlated better with day 1 versus day 5 ifosfamide pharmacokinetics suggesting that the alteration of ifosfamide pharmacology with multiple dosing has a significant effect on drug activity.
引用
收藏
页码:19 / 23
页数:5
相关论文
共 21 条
[1]  
ALLEN LM, 1975, CLIN PHARMACOL THER, V17, P492
[2]  
ALLEN LM, 1976, CANCER TREAT REP, V60, P451
[3]  
BROCK N, 1979, ARZNEIMITTEL-FORSCH, V29-1, P659
[4]  
BRYANT BM, 1980, LANCET, V2, P657
[5]   HIGH-DOSE IFOSFAMIDE WITH MESNA UROPROTECTION - A PHASE-I STUDY [J].
ELIAS, AD ;
EDER, JP ;
SHEA, T ;
BEGG, CB ;
FREI, E ;
ANTMAN, KH .
JOURNAL OF CLINICAL ONCOLOGY, 1990, 8 (01) :170-178
[6]   PRIMING REDUCES THE BONE-MARROW TOXICITY OF CARBOPLATIN [J].
GORE, ME ;
HILLS, CA ;
SIDDIK, ZH ;
SLOANE, JP ;
WINKLEY, AR ;
SMITH, IE ;
MILLAR, JL .
EUROPEAN JOURNAL OF CANCER & CLINICAL ONCOLOGY, 1987, 23 (01) :75-80
[7]  
GOREN MP, 1986, LANCET, V2, P1219
[8]  
LEGHA S, 1989, P AM SOC CLIN ONCOL, V8, P322
[9]   FRACTIONATED IFOSFAMIDE THERAPY PRODUCES A TIME-DEPENDENT INCREASE IN IFOSFAMIDE METABOLISM [J].
LEWIS, LD ;
FITZGERALD, DL ;
HARPER, PG ;
ROGERS, HJ .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1990, 30 (05) :725-732
[10]   IFOSFAMIDE PHARMACOKINETICS AND NEUROTOXICITY [J].
LEWIS, LD ;
MEANWELL, CA .
LANCET, 1990, 335 (8682) :175-176