INFLUENCE OF GLUTATHIONE ADMINISTRATION ON THE DISPOSITION OF FREE AND TOTAL PLATINUM IN PATIENTS AFTER ADMINISTRATION OF CISPLATIN

被引:36
作者
LEONE, R
FRACASSO, ME
SORESI, E
CIMINO, G
TEDESCHI, M
CASTOLDI, D
MONZANI, V
COLOMBI, L
USARI, T
BERNAREGGI, A
机构
[1] BOEHRINGER MANNHEIM ITALIE,RES CTR,VIALE LIBERTA KM 0,750,I-20052 MONZA,ITALY
[2] POLICLIN BORGO ROMA,INST PHARMACOL,VERONA,ITALY
[3] OSPED NIGUARDA CA GRANDA,DIV PNEUMOL A PIAZZA,MILAN,ITALY
关键词
D O I
10.1007/BF00686008
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The kinetics of platinum (Pt) was studied in 12 patients suffering from non-small-cell lung cancer or pleural mesothelioma. Each subject received an infusion of cisplatin (CDDP, 80 mg/m2), and six patients were pretreated with glutathione (GSH, 2.5 g given i. v.) at 15 min prior to the cisplatin infusion. After a 3- to 4-week interval, all patients were given a second course of treatment on the same schedule. A biexponential model was fitted to plasma concentrations of total and ultrafilterable Pt. The excretion of Pt in urine was evaluated during the first 48 h after the CDDP infusion. Following the administration of CDDP alone or with GSH pretreatment, the pharmacokinetic parameters of Pt did not significantly differ between the treatments. Also, the unbound fraction determined at each sampling time did not vary significantly between the treatments. However, it is noteworthy that the mean values obtained for the terminal half-life, the volume of distribution, the renal clearance, the percentage of the dose excreted in the urine, and the mean residence time of total Pt were higher in patients who had been pretreated with GSH, suggesting that GSH might increase both the rate of Pt elimination and the extent of Pt distribution and, as a consequence of the latter, might prolong the residence time of Pt in the body. In addition, the unbound fraction of Pt from the 4th to the 48th h was higher following the first dose of CDDP + GSH than after treatment with CDDP alone. Because of the rather high variability in the values of the parameters obtained, further work is planned using a larger number of patients.
引用
收藏
页码:385 / 390
页数:6
相关论文
共 13 条
[1]   HIGH-DOSE INTRAVENOUS GLUTATHIONE IN MAN - PHARMACOKINETICS AND EFFECTS ON CYST(E)INE IN PLASMA AND URINE [J].
AEBI, S ;
ASSERETO, R ;
LAUTERBURG, BH .
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 1991, 21 (01) :103-110
[2]   REACTION OF PLATINUM(II) ANTITUMOR AGENTS WITH SULFHYDRAL COMPOUNDS AND THE IMPLICATIONS FOR NEPHROTOXICITY [J].
CORDEN, BJ .
INORGANICA CHIMICA ACTA-BIOINORGANIC CHEMISTRY, 1987, 137 (1-2) :125-130
[3]   EFFICACY AND SAFETY OF HIGH-DOSE CISPLATIN AND CYCLOPHOSPHAMIDE WITH GLUTATHIONE PROTECTION IN THE TREATMENT OF BULKY ADVANCED EPITHELIAL OVARIAN-CANCER [J].
DIRE, F ;
BOHM, S ;
ORIANA, S ;
SPATTI, GB ;
ZUNINO, F .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 1990, 25 (05) :355-360
[4]   CISPLATIN PHARMACOKINETICS - APPLICATIONS OF A PHYSIOLOGICAL MODEL [J].
FARRIS, FF ;
DEDRICK, RL ;
KING, FG .
TOXICOLOGY LETTERS, 1988, 43 (1-3) :117-137
[5]  
FRACASSO ME, 1987, DRUGS EXP CLIN RES, V6, P367
[6]  
Gibaldi M, 1982, PHARMACOKINETICS REV, V2nd, P45
[7]  
OZOLS RF, 1985, SEMIN ONCOL, V12, P21
[8]  
ROWLAND M, 1989, CLIN PHARMACOKINET, P140
[9]   GLUTATHIONE AND DETOXIFICATION [J].
TEDESCHI, M ;
BOHM, S ;
DIRE, F ;
ORIANA, S ;
SPATTI, GB ;
TOGNELLA, S ;
ZUNINO, F .
CANCER TREATMENT REVIEWS, 1990, 17 (2-3) :203-208
[10]  
TOSETTI F, 1988, ANTICANCER RES, V8, P381