Document 2881
 DOCN  M94A2881
 TI    Phase I/II trial of oral Panavir for HIV infection.
 DT    9412
 AU    Nagourney RA; Hendler SS; Sanchez RA; Strayer G; Sonne M; Lauermann MW;
       Long Beach Memorial Medical Center, CA 90801-1428.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):203 (abstract no. PB0239). Unique
       Identifier : AIDSLINE ICA10/94369694
 AB    OBJECTIVE: To determine safety, efficacy and bioavailability of Panavir
       (4,4'-isopropylidenedithio-bis-2,6-di-t-butylphenol, specially
       formulated) as an oral HIV drug. METHODS: From July 1992 to February
       1994, 25 HIV+ adults received daily oral Panavir at 200 mg (n = 6), 400
       mg (n = 7) and 800 mg (n = 12). Age range 27-66; 22 male/3 female; CD4 <
       10 to 500; Karnofsky scores 70-100; prior antiretroviral therapy in
       16/25; no other antiretroviral therapy given while on study. Endpoints
       were a) Clinical: CD4, opportunistic infections (OI), AIDS-related
       malignancy (ARM), HIV p24 Ag, weight, Karnofsky score, and Quality of
       Life (QOL); b) Safety/tolerance: cardiac, renal, hepatic, hematologic &
       GI; and c) Bioavailability: steady state drug level (SS) and time to SS.
       RESULTS: Of 25 patients, the initial 19 accrued during 7/92-4/93 with
       median CD4 = 77 [6 of 19 had CD4 < 10]. The trial was revised on 7/93 to
       300 < CD4 > 500 (final 6 accruals). There were no cardiac, renal or
       hepatic toxicities. Mild GI toxicities (flatulence, diarrhea) were seen.
       There were no drug related deaths or serious toxicities. With increasing
       dosage, there appeared to be a trend toward stabilization or slight
       elevations of CD4. Karnofsky score, weight and QOL remained stable or
       declined slowly in the first 19 patients but remained stable in the last
       6. HIV p24 Ag and beta-2-microglobulin varied. While 3 patients
       developed OI, none developed ARM. Dose (SS): 200 mg (12 ug/ml), 400 mg
       (18 ug/ml); 800 mg (26 ug/ml). Time to steady state was 2-3 weeks in
       each case. There was evidence for significant activity against painful
       peripheral neuropathy and against Molluscum contagiosum. DISCUSSION AND
       CONCLUSIONS: Panavir is a well tolerated novel agent for the treatment
       of HIV infection with a unique mode of action related to antioxidant,
       anti-HIV, and possibly anti-apoptotic properties.
 DE    Administration, Oral  Adult  Aged  Antioxidants/ADMINISTRATION &
       DOSAGE/ADVERSE EFFECTS/  PHARMACOKINETICS/THERAPEUTIC USE  Antiviral
       Agents/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/
       PHARMACOKINETICS/*THERAPEUTIC USE  Biological Availability  Female
       Gastrointestinal Diseases/CHEMICALLY INDUCED  Human  HIV
       Infections/*DRUG THERAPY  Male  Middle Age  Probucol/ADMINISTRATION &
       DOSAGE/ADVERSE EFFECTS/PHARMACOKINETICS/  *THERAPEUTIC USE  Treatment
       Outcome  CLINICAL TRIAL  CLINICAL TRIAL, PHASE I  CLINICAL TRIAL, PHASE
       II  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).