Efficacy of the acyclic nucleoside phosphonates (S)-9-(3-fluoro-2-phosphonylmethoxypropyl)adenine (FPMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) against feline immunodeficiency virus

被引:20
|
作者
Hartmann, K
Kuffer, M
Balzarini, J
Naesens, L
Goldberg, M
Erfle, V
Goebel, FD
De Clercq, E
Jindrich, J
Holy, A
Bischofberger, N
Kraft, W
机构
[1] Univ Munich, Med Tierklin 1, D-80539 Munich, Germany
[2] Univ Munich, Inst Physiol, D-80539 Munich, Germany
[3] Univ Munich, Med Poliklin, D-80539 Munich, Germany
[4] Katholieke Univ Leuven, Rega Inst Med Res, B-3001 Louvain, Belgium
[5] GSF, Forschungszentrum Neuherberg, Oberschleissheim, Germany
[6] Acad Sci Czech Republ, Inst Organ Chem & Biochem, Prague, Czech Republic
[7] Gilead Sci Inc, Foster City, CA 94404 USA
关键词
FIV; acyclic nucleoside phosphonates; PMEA; FPMPA; AIDS; chemotherapy;
D O I
10.1097/00042560-199802010-00004
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The acyclic nucleoside phosphonates (S)-9-(3-fluoro-2-phosphonylmethoxypropyl)adenine (FPMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) were evaluated for their efficacy and side effects in a double-blind placebo-controlled trial using naturally occurring feline immunodeficiency virus (FIV)-infected cats. This natural retrovirus animal model is considered highly relevant for the pathogenesis and chemotherapy of HIV in humans. Both PMEA and FPMPA proved effective in ameliorating the clinical symptoms of FIV-infected cats, as measured by several clinical parameters including the incidence and severity of stomatitis, Karnofsky's score, immunologic parameters such as relative and absolute CD4(+) lymphocyte counts, and virologic parameters including proviral DNA levels in peripheral blood mononuclear cells (PBMC) of drug-treated animals, in contrast with PMEA, FPMPA showed no hematologic side effects at a dose that was 2.5-foId higher than PMEA.
引用
收藏
页码:120 / 128
页数:9
相关论文
共 50 条
  • [21] INHIBITORY EFFECT OF 9-(2-PHOSPHONYLMETHOXYETHYL)-ADENINE (PMEA) ON HUMAN AND DUCK HEPATITIS-B VIRUS-INFECTION
    HEIJTINK, RA
    DEWILDE, GA
    KRUINING, J
    BERK, L
    BALZARINI, J
    DECLERCQ, E
    HOLY, A
    SCHALM, SW
    ANTIVIRAL RESEARCH, 1993, 21 (02) : 141 - 153
  • [22] In vitro and in vivo inhibitory activity of the differentiation-inducing agent 9-(2-phosphonylmethoxyethyl)adenine (PMEA) against rat choriocarcinoma
    Hatse, S
    Naesens, L
    Degrève, B
    Vandeputte, M
    Waer, M
    De Clercq, E
    Balzarini, J
    PURINE AND PYRIMIDINE METABOLISM IN MAN IX, 1998, 431 : 605 - 609
  • [23] Comparison of the Disposition of Ester Prodrugs of the Antiviral Agent 9-(2-phosphonylmethoxyethyl)adenine [PMEA] in Caco-2 Monolayers
    P. Annaert
    G. Gosselin
    A. Pompon
    S. Benzaria
    G. Valette
    J.-L. Imbach
    L. Naesens
    S. Hatse
    E. de Clercq
    G. Van den Mooter
    R. Kinget
    P. Augustijns
    Pharmaceutical Research, 1998, 15 : 239 - 245
  • [24] Efficacy of 9-(2-phosphonylmethoxyethyl)adenine treatment against chronic simian immunodeficiency virus infection in macaques (vol 171, pg 1338, 1995)
    Tsai, CC
    Follis, KE
    Sabo, A
    Grant, R
    Bischofberger, N
    JOURNAL OF INFECTIOUS DISEASES, 1996, 173 (01): : 277 - 277
  • [25] SYNTHESIS AND ANTI-HUMAN IMMUNODEFICIENCY VIRUS-1(HIV-1) ACTIVITY OF 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE (1)AND ITS REGIOISOMER 3-(2-PHOSPHONYLMETHOXYETHYL)ADENINE(2)
    Xiao Hui LIU
    Lin WANG
    Bao He GUAN
    Man KONG Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Meical CollegeBijing Xing Quan ZHANG
    Pei Zhen TAo
    Hong Shan CHEN Institute of Medicinal BiotechnologyChinese Academy of
    ChineseChemicalLetters, 1995, (08)
  • [26] Comparison of the disposition of ester prodrugs of the antiviral agent 9-(2-phosphonylmethoxyethyl)adenine [PMEA] in Caco-2 monolayers
    Annaert, P
    Gosselin, G
    Pompon, A
    Benzaria, S
    Valette, G
    Imbach, JL
    Naesens, L
    Hatse, S
    de Clercq, E
    Van den Mooter, G
    Kinget, R
    Augustijns, P
    PHARMACEUTICAL RESEARCH, 1998, 15 (02) : 239 - 245
  • [27] Novel hepatotrophic prodrugs of the antiviral nucleoside 9-(2-phosphonylmethoxyethyl)adenine with improved pharmacokinetics and antiviral activity
    Biessen, EAL
    Valentijn, ARPM
    De Vrueh, RLA
    Van de Bilt, E
    Sliedregt, LAJM
    Prince, P
    Bijsterbosch, MK
    Van Boom, JH
    Van der Marel, GA
    Abrahams, PJ
    Van Berkel, TJC
    FASEB JOURNAL, 2000, 14 (12): : 1784 - 1792
  • [28] 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
  • [29] Synthesis and anti-human immunodeficiency virus-1(HIV-1) activity of 9-(2-phosphonylmethoxyethyl)adenine (1) and its regioisomer 3-(2-phosphonylmethoxyethyl)adenine (2)
    Liu, XH
    Wang, L
    Guan, BH
    Kong, M
    Zhang, XQ
    Tao, PZ
    Chen, HS
    CHINESE CHEMICAL LETTERS, 1995, 6 (08) : 669 - 672
  • [30] Synthesis of a lipophilic prodrug of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and its incorporation into a hepatocyte-specific lipidic carrier
    de Vrueh, RLA
    Rump, ET
    Sliedregt, LAJM
    Biessen, EAL
    van Berkel, TJC
    Bijsterbosch, MK
    PHARMACEUTICAL RESEARCH, 1999, 16 (08) : 1179 - 1185