Document 1107
 DOCN  M94A1107
 TI    Tolerance and pharmacokinetics of oral foscarnet in HIV seropositives.
 DT    9412
 AU    Youle MS; Noormohamed FH; Higgs CJ; Gazzard BG; Nelson M; Martin-Munley
       S; Lant A.F. HIV Unit Kobler Centre London, UK.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(2):207 (abstract no. PB0840). Unique
       Identifier : AIDSLINE ICA10/94371468
 AB    OBJECTIVE: To assess the tolerance and pharmacokinetic profile of an
       oral formulation of foscarnet sodium (oral FOS) in HIV seropositives.
       METHOD: 15 HIV-infected subjects (3 with AIDS; mean T4 count 528/mm3,
       range 130-1280/mm3) were enrolled. Doses of oral FOS were 90mg/kg q24h
       (N = 6); 90mg/kg q12h (N = 6) and 180mg/kg q24h (N = 3). After a 7 day
       washout period (day 15) each subject received an intravenous (i.v.) dose
       of FOS (90mg/kg) over 2 hours. Subjects remained on their respective
       concomitant medication, except on PK days ie. 1, 8 and 15 of the study.
       Renal function was monitored for 8 hours post-dose, using
       51chromium-EDTA. RESULTS: 13 subjects completed the 15 day study period.
       One withdrew due to suspected appendicitis and a second for marked
       abdominal pain. During the oral phase 90% developed frequency of bowel
       opening and watery diarrhoea which persisted for the duration of oral
       dosing. No laboratory abnormalities developed during the study. Mean
       plasma concentrations, AUC and urine recovery increased from day 1-8 (p
       < 0.05), the mean accumulation ratio rose to between 1.5 and 2.2 after 8
       days on oral FOS. No significant differences were seen in the
       elimination half life (t1/2z) on days 1 or 8. C max (day 8) for all
       doses of oral FOS ranged from 61.0-109 microM compared to 788.5-881.1
       microM for i.v. FOS. AUC (day 8) for all doses of oral FOS ranged from
       637-1058 microM h compared to 3239-3661 microM h for iv FOS Total body
       clearance, following iv FOS was 99 +/- 5ml/min whilst volume of
       distribution, at steady state was 22 +/- 11. 93% of dose administered
       i.v. was excreted within 24hrs. CONCLUSION: This formulation of oral FOS
       was not well tolerated at the doses administered and only achieved 10%
       bioavailability compared to iv FOS. Further formulations are being
       developed to improve on this.
 DE    Administration, Oral  Biological Availability  Foscarnet/ADMINISTRATION
       & DOSAGE/ADVERSE EFFECTS/  *PHARMACOKINETICS  Half-Life  Human  HIV
       Infections/*DRUG THERAPY  MEETING ABSTRACT

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