EFFICACY OF (S)-1-(3-HYDROXY-2-PHOSPHONYLMETHOXYPROPYL)-CYTOSINE AND 9-(1,3-DIHYDROXY-2-PROPOXYMETHYL)-GUANINE IN THE TREATMENT OF INTRACEREBRAL MURINE CYTOMEGALOVIRUS INFECTIONS IN IMMUNOCOMPETENT AND IMMUNODEFICIENT MICE

被引:39
作者
NEYTS, J
SOBIS, H
SNOECK, R
VANDEPUTTE, M
DECLERCQ, E
机构
[1] Rega Institute for Medical Research, Leuven Catholic University, Leuven, B-3000
关键词
D O I
10.1007/BF01967257
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
The efficacy of HPMPC and DHPG against systemic and intracerebral murine cytomegalovirus (MCMV) infections was examined in immunocompetent NMRI mice and in mice with severe combined immunodeficiency (SCID). HPMPC proved to be far superior to DHPG in preventing mortality and growth retardation in MCMV-infected NMRI mice even when given as a single dose on the day of infection. In intraperitoneally infected SCID mice, HPMPC administered as a single dose of 2, 10,20 or 50 mg/kg per week increased the survival period of the mice by 22, 49, 77 and 156 days, respectively. In contrast, DHPG at daily doses of 10, 20 or 50 mg/kg for five consecutive days every week did not delay death by more than 13, 17 and 21 days, respectively. About one week before the MCMV-infected SCID mice (treated with either DHPG or HPMPC) died, they developed signs of neurological disease and intranuclear inclusion-bearing cells were found in their brains. The virus that was recovered from the brains of these mice did not prove to be resistant to HPMPC or DHPG. Only the virus recovered from the brains of mice treated with HPMPC at a dosage of 50 mg/kg/week had a slightly decreased susceptibility to HPMPC. When HPMPC (50 mg/kg for 4 consecutive days) was administered to SCID mice at the time when neurological symptoms became apparent, death of the animals could be delayed by another 35 to 40 days.
引用
收藏
页码:269 / 279
页数:11
相关论文
共 56 条
[11]   EFFICACY OF (S)-1-(3-HYDROXY-2-PHOSPHONYLMETHOXYPROPYL)CYTOSINE IN VARIOUS MODELS OF HERPES-SIMPLEX VIRUS-INFECTION IN MICE [J].
DECLERCQ, E ;
HOLY, A .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1991, 35 (04) :701-706
[12]  
DECLERCQ E, 1987, ANTIVIR RES, V8, P261
[13]   A NOVEL SELECTIVE BROAD-SPECTRUM ANTI-DNA VIRUS AGENT [J].
DECLERCQ, E ;
HOLY, A ;
ROSENBERG, I ;
SAKUMA, T ;
BALZARINI, J ;
MAUDGAL, PC .
NATURE, 1986, 323 (6087) :464-467
[14]   PREVALENCE OF RESISTANCE IN PATIENTS RECEIVING GANCICLOVIR FOR SERIOUS CYTOMEGALOVIRUS-INFECTION [J].
DREW, WL ;
MINER, RC ;
BUSCH, DF ;
FOLLANSBEE, SE ;
GULLETT, J ;
MEHALKO, SG ;
GORDON, SM ;
OWEN, WF ;
MATTHEWS, TR ;
BUHLES, WC ;
DEARMOND, B .
JOURNAL OF INFECTIOUS DISEASES, 1991, 163 (04) :716-719
[15]   CYTOMEGALO-VIRUS INFECTION OF THE ADULT NERVOUS-SYSTEM [J].
DUCHOWNY, M ;
CAPLAN, L ;
SIBER, G .
ANNALS OF NEUROLOGY, 1979, 5 (05) :458-461
[16]   PROGRESSIVE DISEASE DUE TO GANCICLOVIR-RESISTANT CYTOMEGALO-VIRUS IN IMMUNOCOMPROMISED PATIENTS [J].
ERICE, A ;
CHOU, S ;
BIRON, KK ;
STANAT, SC ;
BALFOUR, HH ;
JORDAN, MC .
NEW ENGLAND JOURNAL OF MEDICINE, 1989, 320 (05) :289-293
[17]  
EWING S, 1991, KLIN WOCHENSCHR, V69, P449
[18]   GANCICLOVIR - A REVIEW OF ITS ANTIVIRAL ACTIVITY, PHARMACOKINETIC PROPERTIES AND THERAPEUTIC EFFICACY IN CYTOMEGALOVIRUS INFECTIONS [J].
FAULDS, D ;
HEEL, RC .
DRUGS, 1990, 39 (04) :597-638
[19]   HUMAN PHARMACOKINETICS OF THE ANTIVIRAL DRUG DHPG [J].
FLETCHER, C ;
SAWCHUK, R ;
CHINNOCK, B ;
DEMIRANDA, P ;
BALFOUR, HH .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1986, 40 (03) :281-286
[20]   SEXUALLY-TRANSMITTED DISEASES IN MOTHERS OF NEONATES WITH CONGENITAL CYTOMEGALOVIRUS-INFECTION [J].
FOWLER, KB ;
PASS, RF .
JOURNAL OF INFECTIOUS DISEASES, 1991, 164 (02) :259-264