PHARMACOKINETIC, SAFETY, AND ANTIVIRAL PROFILES OF ORAL GANCICLOVIR IN PERSONS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS - A PHASE I/II STUDY

被引:84
作者
SPECTOR, SA
BUSCH, DF
FOLLANSBEE, S
SQUIRES, K
LALEZARI, JP
JACOBSON, MA
CONNOR, JD
JUNG, D
SHADMAN, A
MASTRE, B
BUHLES, W
DREW, WL
DANKNER, WM
MEIXNER, L
FREEMAN, WR
DYNER, TS
FREEMAN, E
MORTILLARO, G
GLUTZER, E
BUSH, T
COLEMAN, R
机构
[1] UNIV CALIF SAN FRANCISCO,MT ZION MED CTR,DAVIES MED CTR,CALIF PACIFIC MED CTR,SAN FRANCISCO,CA 94120
[2] SYNTEX INC,RES,PALO ALTO,CA
[3] CORNELL UNIV,MED CTR,NEW YORK,NY 10021
关键词
D O I
10.1093/infdis/171.6.1431
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A phase I/II study evaluated the pharmacokinetics, tolerability, and antiviral activity of oral ganciclovir in persons infected with human immunodeficiency virus (HIV). Oral bioavailability ranged from 2.6% to 7.3%. The mean maximum serum concentration achieved at 1000 mg every 8 h was 1.11 mu g/mL, and mean trough level was 0.54 mu g/mL. The time to maximum serum drug concentration was 1.0-2.9 h, with a serum half-life of 3.0-7.3 h, suggesting prolonged oral absorption. Serious adverse events were uncommon. Decreased cytomegalovirus (CMV) shedding was observed from all sites. The median days (by dosage) to retinitis progression assessed by retinal examination after initiation of oral ganciclovir were 62 (1000 mg every 8 h), 148 (500 mg every 3 h), 75 (750 mg every 3 h), 148 (1000 mg every 3 h), and 139 (2000 mg every 8 h). Thus, oral ganciclovir has pharmacokinetic, toxicity, and antiviral profiles that may prove beneficial for both maintenance therapy of CMV retinitis and prevention of CMV disease in HIV-infected persons.
引用
收藏
页码:1431 / 1437
页数:7
相关论文
共 23 条
[1]   THE DIAGNOSIS OF CYTOMEGALO-VIRUS RETINITIS [J].
BLOOM, JN ;
PALESTINE, AG .
ANNALS OF INTERNAL MEDICINE, 1988, 109 (12) :963-969
[2]   CYTOMEGALO-VIRUS INFECTION IN PATIENTS WITH AIDS [J].
DREW, WL .
JOURNAL OF INFECTIOUS DISEASES, 1988, 158 (02) :449-456
[3]   INCIDENCE AND NATURAL-HISTORY OF CYTOMEGALOVIRUS DISEASE IN PATIENTS WITH ADVANCED HUMAN-IMMUNODEFICIENCY-VIRUS DISEASE TREATED WITH ZIDOVUDINE [J].
GALLANT, JE ;
MOORE, RD ;
RICHMAN, DD ;
KERULY, J ;
CHAISSON, RE ;
BARTLETT, J ;
MCAVINUE, S ;
BRYSON, Y ;
COHEN, H ;
FISCHL, M ;
BOLIN, T ;
KESSLER, H ;
BURROUGH, Y ;
MILDVAN, D ;
FOX, A ;
RICHMAN, D ;
FREEMAN, B ;
SIMON, G ;
GRABOWY, KW ;
CHERNOFF, D ;
DUFF, P ;
THOMPSON, S ;
BARRETT, K ;
AWE, R ;
CHAPMAN, R ;
LEONARD, S ;
BAINES, L ;
TURNER, P ;
HAWKINS, M ;
MURRAY, H ;
BOWERS, J ;
LANE, C ;
TILSON, H ;
ANDREWS, E ;
SMILEY, L .
JOURNAL OF INFECTIOUS DISEASES, 1992, 166 (06) :1223-1227
[4]   EARLY TREATMENT WITH GANCICLOVIR TO PREVENT CYTOMEGALOVIRUS DISEASE AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION [J].
GOODRICH, JM ;
MORI, M ;
GLEAVES, CA ;
DUMOND, C ;
CAYS, M ;
EBELING, DF ;
BUHLES, WC ;
DEARMOND, B ;
MEYERS, JD .
NEW ENGLAND JOURNAL OF MEDICINE, 1991, 325 (23) :1601-1607
[5]   A CONTROLLED TRIAL OF TRIMETHOPRIM SULFAMETHOXAZOLE OR AEROSOLIZED PENTAMIDINE FOR SECONDARY PROPHYLAXIS OF PNEUMOCYSTIS-CARINII PNEUMONIA IN PATIENTS WITH THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME - AIDS CLINICAL-TRIALS GROUP PROTOCOL-021 [J].
HARDY, WD ;
FEINBERG, J ;
FINKELSTEIN, DM ;
POWER, ME ;
HE, W ;
KACZKA, C ;
FRAME, PT ;
HOLMES, M ;
WASKIN, H ;
FASS, RJ ;
POWDERLY, WG ;
STEIGBIGEL, RT ;
ZUGER, A ;
HOLZMAN, RS .
NEW ENGLAND JOURNAL OF MEDICINE, 1992, 327 (26) :1842-1848
[6]   A CONTROLLED-STUDY OF INHALED PENTAMIDINE FOR PRIMARY PREVENTION OF PNEUMOCYSTIS-CARINII PNEUMONIA [J].
HIRSCHEL, B ;
LAZZARIN, A ;
CHOPARD, P ;
OPRAVIL, M ;
FURRER, HJ ;
RUTTIMANN, S ;
VERNAZZA, P ;
CHAVE, JP ;
ANCARANI, F ;
GABRIEL, V ;
HEALD, A ;
KING, R ;
MALINVERNI, R ;
MARTIN, JL ;
MERMILLOD, B ;
NICOD, L ;
SIMONI, L ;
VIVIRITO, MC ;
ZERBONI, R .
NEW ENGLAND JOURNAL OF MEDICINE, 1991, 324 (16) :1079-1083
[7]   TOXICITY OF COMBINED GANCICLOVIR AND ZIDOVUDINE FOR CYTOMEGALOVIRUS DISEASE ASSOCIATED WITH AIDS - AN AIDS CLINICAL-TRIALS GROUP-STUDY [J].
HOCHSTER, H ;
DIETERICH, D ;
BOZZETTE, S ;
REICHMAN, RC ;
CONNOR, JD ;
LIEBES, L ;
SONKE, RL ;
SPECTOR, SA ;
VALENTINE, F ;
PETTINELLI, C ;
RICHMAN, DD .
ANNALS OF INTERNAL MEDICINE, 1990, 113 (02) :111-117
[8]  
JABS DA, 1989, OPHTHALMOLOGY, V96, P1092
[9]   CYTOMEGALO-VIRUS RETINITIS AND ACQUIRED IMMUNODEFICIENCY SYNDROME [J].
JABS, DA ;
ENGER, C ;
BARTLETT, JG .
ARCHIVES OF OPHTHALMOLOGY, 1989, 107 (01) :75-80
[10]   FOSCARNET TREATMENT OF CYTOMEGALO-VIRUS RETINITIS IN PATIENTS WITH THE ACQUIRED IMMUNODEFICIENCY SYNDROME [J].
JACOBSON, MA ;
ODONNELL, JJ ;
MILLS, J .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1989, 33 (05) :736-741