SINGLE-DOSE ADMINISTRATION OF 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE (PMEA) AND 9-(2-PHOSPHONYLMETHOXYETHYL)-2,6-DIAMINOPURINE (PMEDAP) IN THE PROPHYLAXIS OF RETROVIRUS INFECTION INVIVO

被引:35
|
作者
NAESENS, L [1 ]
BALZARINI, J [1 ]
DECLERCQ, E [1 ]
机构
[1] CATHOLIC UNIV LEUVEN,REGA INST MED RES,MINDERBROEDERSSTR 10,B-3000 LOUVAIN,BELGIUM
关键词
HUMAN IMMUNODEFICIENCY VIRUS; HIV; MOLONEY MURINE SARCOMA VIRUS; MSV; SINGLE DOSE ADMINISTRATION; 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE; PMEA; 9-(2-PHOSPHONYLMETHOXYETHYL)-2,6-DIAMINOPURINE, PMEDAP;
D O I
10.1016/0166-3542(91)90058-Y
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
9-(2-Phosphonylmethoxyethyl)adenine (PMEA) and 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) are selectively inhibitory to human immunodeficiency virus and other retroviruses. We have now investigated the effects of different PMEA and PMEDAP treatment schedules in newborn mice infected with Moloney murine sarcoma virus (MSV). Administration of a single dose of PMEA or PMEDAP on the day of MSV inoculation conferred a greater protective effect against MSV-induced tumor formation than when this dose was divided over two, four or seven injections per week. Also, the therapeutic index of PMEA and PMEDAP was increased if administered as a single dose. Furthermore, PMEA and PMEDAP afforded a marked antiviral protection if administered within one day before MSV infection. Thus, single doses of PMEA or PMEDAP, when administered shortly before or after MSV infection, appear to be effective in preventing the manifestations of the retroviral disease.
引用
收藏
页码:53 / 64
页数:12
相关论文
共 50 条
  • [41] Carrier-mediated delivery improves the efficacy of 9-(2-phosphonylmethoxyethyl)adenine against hepatitis B virus
    Bijsterbosch, MK
    Ying, CX
    De Vrueh, RLA
    De Clercq, E
    Biessen, EAL
    Neyts, J
    Van Berkel, TJC
    MOLECULAR PHARMACOLOGY, 2001, 60 (03) : 521 - 527
  • [42] Novel mutations in the herpes simplex virus type 1 (HSV-1) DNA polymerase associated with resistance to foscarnet (PFA) and 2-phosphonylmethoxyethyl (PME) derivatives of adenine (PMEA) and 2,6-diaminopurine (PMEDAP).
    Andrei, G
    Fiten, P
    De Clercq, E
    Opdenakker, G
    Snoeck, R
    ANTIVIRAL RESEARCH, 2002, 53 (03) : A57 - A57
  • [43] EVALUATION OF 9-(2-PHOSPHONYLMETHOXYETHYL) ADENINE THERAPY FOR FELINE IMMUNODEFICIENCY VIRUS USING A QUANTITATIVE POLYMERASE CHAIN-REACTION
    PHILPOTT, MS
    EBNER, JP
    HOOVER, EA
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 1992, 35 (1-2) : 155 - 166
  • [44] Inhibition of duck hepatitis B virus replication by 9-(2-phosphonylmethoxyethyl)adenine, an acyclic phosphonate nucleoside analogue
    Nicoll, AJ
    Colledge, DL
    Toole, JJ
    Angus, PW
    Smallwood, RA
    Locarnini, SA
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1998, 42 (12) : 3130 - 3135
  • [45] Potent antitumor activity of the acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine in choriocarcinoma-bearing rats
    Hatse, S
    Naesens, L
    Degrève, B
    Segers, C
    Vandeputte, M
    Waer, M
    De Clercq, E
    Balzarini, J
    INTERNATIONAL JOURNAL OF CANCER, 1998, 76 (04) : 595 - 600
  • [46] Potent differentiation-inducing properties of the antiretroviral agent 9-(2-phosphonylmethoxyethyl) adenine (PMEA) in the rat choriocarcinoma (RCHO) tumor cell model
    Hatse, S
    Naesens, L
    De Clercq, E
    Balzarini, J
    BIOCHEMICAL PHARMACOLOGY, 1998, 56 (07) : 851 - 859
  • [47] INDUCTION OF ERYTHROID-DIFFERENTIATION OF HUMAN LEUKEMIA K562 CELLS BY THE ACYCLIC NUCLEOSIDE PHOSPHONATE 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE (PMEA)
    HATSE, S
    BALZARINI, J
    DECLERCQ, E
    NUCLEOSIDES & NUCLEOTIDES, 1995, 14 (3-5): : 649 - 652
  • [48] ORAL BIOAVAILABILITY OF THE ANTIRETROVIRAL AGENT 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE (PMEA) FROM 3-FORMULATIONS OF THE PRODRUG BIS(PIVALOYLOXYMETHYL)-PMEA IN FASTED MALE CYNOMOLGUS MONKEYS
    CUNDY, KC
    FISHBACK, JA
    SHAW, JP
    LEE, ML
    SOIKE, KF
    VISOR, GC
    LEE, WA
    PHARMACEUTICAL RESEARCH, 1994, 11 (06) : 839 - 843
  • [49] THE HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) INHIBITOR 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE (PMEA) IS A STRONG INDUCER OF DIFFERENTIATION OF SEVERAL TUMOR-CELL LINES
    BALZARINI, J
    VERSTUYF, A
    HATSE, S
    GOEBELS, J
    SOBIS, H
    VANDEPUTTE, M
    DECLERCQ, E
    INTERNATIONAL JOURNAL OF CANCER, 1995, 61 (01) : 130 - 137
  • [50] HIV-1 DEVELOPS REDUCED SENSITIVITY TO 9-(2-PHOSPHONYLMETHOXYETHYL) ADENINE (PMEA) IN-VITRO THROUGH ACQUISITION OF K65R
    SOGOCIO, KM
    ANDERSON, B
    KAVLICK, M
    SAVILLE, W
    WAINBERG, MA
    CHERRINGTON, JM
    MITSUYA, H
    YARCHOAN, R
    AIDS RESEARCH AND HUMAN RETROVIRUSES, 1995, 11 : S164 - S164