Effect of leflunomide and cidofovir on replication of BK-virus in an in vitro culture system

被引:128
作者
Farasati, NA
Shapiro, R
Vats, A
Randhawa, P
机构
[1] Univ Pittsburgh, Montefiore Hosp, UPMC, Dept Pathol,Div Transplantat Pathol, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA 15213 USA
[3] Childrens Hosp Pittsburgh, Dept Pediat Nephrol, Pittsburgh, PA 15213 USA
关键词
cidofovir; leflunomid; BK virus; culture;
D O I
10.1097/01.TP.0000149338.97084.5F
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Cidofovir and Leflunomide are used empirically in the treatment of BK virus nephropathy. The aim of this study is to quantify the antiviral activity of these drugs. Methods. BK virus was grown in a cell-culture system. The rate of viral replication in the presence or absence of the drug being tested was assessed using a quantitative polymerase chain reaction assay. Results. The inhibitory concentration, effective concentration, and selectivity index for Leflunomide are 39.7 +/- 6.9, 11.3 +/- 2.8, and 3.8 +/- 0.8 mug/mL, respectively. For Cidofovir, these indices were, respectively, 63.9 +/- 17.2, 36.3 +/- 11.7, and 2.3 +/- 0.8 mug/mL. Conclusions. The in vitro activity of Cidofovir and Leflunomide is modest, and the selectivity index is low. There is a need to develop more effective and less toxic anti-BK virus drugs for clinical use.
引用
收藏
页码:116 / 118
页数:3
相关论文
共 15 条
[1]   Treatment of polyomavirus infection with cidofovir in a renal-transplant recipient [J].
Bjorang, O ;
Tveitan, H ;
Midtvedt, K ;
Broch, LU ;
Scott, H ;
Andresen, PA .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2002, 17 (11) :2023-2025
[2]   Clinical pharmacokinetics of 1-[((S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl]cytosine in human immunodeficiency virus-infected patients [J].
Cundy, KC ;
Barditch-Crovo, P ;
Petty, BG ;
Ruby, A ;
Redpath, M ;
Jaffe, HS ;
Lietman, PS .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1999, 43 (02) :271-277
[3]   Human polyoma virus in renal allograft biopsies: Morphological findings and correlation with urine cytology [J].
Drachenberg, CB ;
Beskow, CO ;
Cangro, CB ;
Bourquin, PM ;
Simsir, A ;
Fink, J ;
Weir, MR ;
Klassen, DK ;
Bartlett, ST ;
Papadimitriou, JC .
HUMAN PATHOLOGY, 1999, 30 (08) :970-977
[4]   ANTIVIRAL ACTIVITY OF GYRASE INHIBITORS NORFLOXACIN, COUMERMYCIN-A1 AND NALIDIXIC-ACID [J].
FERRAZZI, E ;
PERACCHI, M ;
BIASOLO, MA ;
FAGGIONATO, O ;
STEFANELLI, S ;
PALU, G .
BIOCHEMICAL PHARMACOLOGY, 1988, 37 (09) :1885-1886
[5]   Polyomavirus BK [J].
Hirsch, HH ;
Steiger, J .
LANCET INFECTIOUS DISEASES, 2003, 3 (10) :611-623
[6]  
Josephson MA, 2003, J AM SOC NEPHROL, V14, p43A
[7]   Inhibition of herpes simplex virus type 1 by the experimental immunosuppressive agent leflunomide [J].
Knight, DA ;
Hejmanowski, AQ ;
Dierksheide, JE ;
Williams, JW ;
Chong, ASF ;
Waldman, WJ .
TRANSPLANTATION, 2001, 71 (01) :170-174
[8]  
Naesens L, 2001, Herpes, V8, P12
[9]  
PIETROPAOLO V, 1995, MICROBIOLOGICA, V18, P341
[10]   Nephropathy due to polyomavirus type BK. [J].
Randhawa, PS ;
Demetris, AJ .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 342 (18) :1361-1363