       Document 0006
 DOCN  M95B0006
 TI    Effect of fluconazole on pharmacokinetics of 2',3'-dideoxyinosine in
       persons seropositive for human immunodeficiency virus.
 DT    9511
 AU    Bruzzese VL; Gillum JG; Israel DS; Johnson GL; Kaplowitz LG; Polk RE;
       School of Medicine, Virginia Commonwealth University/Medical; College of
       Virginia, Richmond, VA 23298-0533, USA.
 SO    Antimicrob Agents Chemother. 1995 May;39(5):1050-3. Unique Identifier :
       AIDSLINE MED/95351740
 AB    Fluconazole inhibits cytochrome P-450-mediated enzymatic metabolism of
       several drugs. Since hepatic metabolism is partially responsible for
       2',3'-dideoxyinosine (didanosine or ddI) elimination, fluconazole
       therapy may lead to increased ddI concentrations in serum and subsequent
       concentration-dependent adverse effects. The purpose of this study was
       to determine if ddI pharmacokinetics are influenced by a 7-day course of
       oral fluconazole. Twelve adults with human immunodeficiency virus (HIV)
       who had received a constant dosage of ddI for at least 2 weeks were
       investigated. On study day 1, multiple serum samples for determination
       of ddI concentrations were obtained over 12 h. Then subjects received a
       7-day course of oral fluconazole (200 mg every 12 h for two doses and
       then 200 mg once daily for 6 days) while ddI therapy continued.
       Following the last dose of fluconazole, serum samples for determination
       of ddI concentrations were again obtained over 12 h. ddI concentrations
       in serum were analyzed by radioimmunoassay. In contrast to previously
       published data, there was marked between-subject variability in ddI
       areas under the concentration-time curve, even when the dose was
       normalized for weight. No significant differences were found between
       mean ddI areas under the concentration-time curve from 0 to 12 h on
       study day 1 (1,528 +/- 902 ngx.hr/ml) and following fluconazole
       treatment (1,486 +/- 649 ngx.hr/ml) .There were no significant
       differences in other pharmacokinetic parameters, such as ddI peak
       concentrations in serum (971 +/- 509 and 942 +/- 442 ng/ml) or
       half-lives (80 +/- 32 and 85 +/- 21 min.) before and after fluconazole
       treatment, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 DE    Adult  Didanosine/ADVERSE EFFECTS/*PHARMACOKINETICS  Drug Interactions
       Female  Fluconazole/ADVERSE EFFECTS/*PHARMACOLOGY  Half-Life  Human  HIV
       Seropositivity/*METABOLISM  Male  Middle Age  Radioimmunoassay  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  CLINICAL TRIAL  JOURNAL
       ARTICLE

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

