EARLY PHARMACOKINETIC AND CLINICAL-RESULTS FROM A NONCOMPARATIVE MULTICENTER TRIAL OF AMPHOTERICIN-B ENCAPSULATED IN A SMALL UNILAMELLAR LIPOSOME (AMBISOME(R))

被引:22
作者
TOLLEMAR, J [1 ]
RINGDEN, O [1 ]
RICCI, P [1 ]
TURA, S [1 ]
MEUNIER, F [1 ]
KLASTERSKY, J [1 ]
VIVIANI, M [1 ]
GORIN, NC [1 ]
FENAUX, P [1 ]
KUSE, ER [1 ]
PRENTICE, HG [1 ]
BLANCHE, S [1 ]
CLUMECK, N [1 ]
HAY, R [1 ]
FRASCHINI, F [1 ]
STOUTENBEEAK, C [1 ]
MEUSERS, P [1 ]
SCHROYENS, W [1 ]
GOLDSTONE, A [1 ]
LINDENMANN, A [1 ]
RODENHUIS, S [1 ]
WALDNER, R [1 ]
ZITTOUN, R [1 ]
PIERCE, P [1 ]
ALEMELEH, R [1 ]
ABECASSIS, M [1 ]
GOUVEIA, A [1 ]
ZIRKULNIG, R [1 ]
机构
[1] HUDDINGE HOSP,DEPT CLIN IMMUNOL,S-14186 HUDDINGE,SWEDEN
来源
DRUG INVESTIGATION | 1992年 / 4卷 / 03期
关键词
D O I
10.1007/BF03258404
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
AmBisome (R) 0.5 to 4 mg/kg/day, a small unilamellar liposome encapsulating amphotericin B, was administered to 59 patients with mycologically confirmed infections (36 had candidiasis, 18 had aspergillosis and 5 had other infections). Of the treated patients, 37 (63%) were considered cured, 9 (15%) improved, and 13 (22%) failed to respond. The response rate in patients with candidiasis was 83% (30/36) compared with 61% (11/18) for aspergillosis (not significant). All other mycoses were cured or improved. 80% (16) of 20 evaluable patients were cured or improved when AmBisome (R) was used because of the prior failure of conventional amphotericin B in a compassionate basis trial. AmBisome (R) at dose levels ranging between 2 and 4 mg/kg produced peak plasma levels ranging from 16.0 +/- 6.7 to 46.0 +/- 10.2 mg/L. Tissue levels were highest in liver and spleen and were low in kidney and lung. Side effects associated with AmBisome (R) included increases in serum creatinine (n = 9) and alkaline phosphatase (2), hypokalaemia (3) and pancreatitis (1).
引用
收藏
页码:232 / 238
页数:7
相关论文
共 25 条
[1]  
Buchard K.W., Minor L.B., Slotman G.J., Gann D.S., Fungal sepsis in surgical patients, Archives of Surgery, 118, pp. 217-221, (1983)
[2]  
Christiansen K.J., Bernard E.M., Gold J.W.M., Artrong D., Distribution and activity of amphotericin B in humans, Journal of Infectious Diseases, 152, pp. 1037-1043, (1985)
[3]  
Clift R.A., Candidiasis in the transplant patient, American Journal of Medicine, 77, pp. 34-37, (1984)
[4]  
Colonna J.O., Winston D.J., Brill J.E., Goldstein L.I., Hoff M.P., Et al., Infectious complications in liver transplantation, Archives of Surgery, 123, pp. 360-364, (1988)
[5]  
Graybill J.R., Craven P.C., Taylor R.L., Willia D.M., Magee W.E., Treatment of murine cryptococcosis with liposome-associated amphotericin B, Journal of Infectious Diseases, 145, pp. 748-752, (1982)
[6]  
Hansen R.H., Reinerio N., Sohnle P.G., Abra R.A., Ritch P.S., Et al., Ketoconazole in the prevention of candidiasis in patients with cancer, Archives of Internal Medicine, 147, pp. 710-712, (1987)
[7]  
Hopfer R.L., Mills K., Mehta R., Lopez-Berestein G., Fainstein V., Et al., In vitro antifungal activities of amphotericin B and liposome encapsulated amphotericin B, Antimicrobial Agents and Chemotherapy, 215, pp. 387-389, (1984)
[8]  
Jones P.G., Kauffmann C.A., McAuliffe L.S., Liespman M.K., Bergman A.G., Efficacy of ketoconazole versus nystatin in prevention of fungal infections in neutropenic patients, Archives of Internal Medicine, 144, pp. 549-551, (1984)
[9]  
Lopez-Berestein G., Bodey G.P., Fainstein V., Keating M., Frankel L.S., Et al., Treatment of systemic fungal infections with liposomal amphotericin B, Archives of Internal Medicine, 149, pp. 2533-2536, (1989)
[10]  
Lopez-Berestein G., Bodey G.P., Frankel L.S., Mehta K., Treatment of hepatosplenic candidiasis with liposomal amphotericin B, Journal of Clinical Oncology, 5, pp. 310-317, (1987)