Document 1217
 DOCN  M9591217
 TI    A phase I evaluation of concomitant rifabutin and didanosine in
       symptomatic HIV-infected patients.
 DT    9509
 AU    Sahai J; Narang PK; Hawley-Foss N; Li RC; Kamal M; Cameron DW; Clinical
       Investigation Unit, Ottawa General Hospital, Ontario,; Canada.
 SO    J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Jul 1;9(3):274-9.
       Unique Identifier : AIDSLINE MED/95308203
 AB    It has been suggested that didanosine (ddI) may undergo hepatic
       metabolism. Rifabutin is an inducer of drug metabolism. Fifteen human
       immunodeficiency virus-infected patients whose conditions were
       stabilized on twice-daily doses of ddI participated in a Phase I,
       open-label, pharmacokinetic and safety drug interaction study between
       rifabutin and ddI. Twelve patients completed the study. All patients
       received their regular ddI dose (167-375 mg) on day 1. On days 2-13 they
       received once-daily rifabutin (600 mg, three patients; 300 mg, nine
       patients) with their regular twice-daily ddI regimen. On days 14-16 they
       received rifabutin alone. Serial blood and urine samples were collected
       for 12 h on day 1 and for 24 h on days 13 and 16, and safety evaluations
       were made throughout the study. Average day 1/day 13 ddI pharmacokinetic
       ratios and 95% confidence interval values for Cmax, AUC0-infinity,
       Cls/F, and t 1/2, lambda z were 1.17 (0.96-1.38), 1.13 (0.99-1.27), 0.91
       (0.81-1.01), and 0.97 (0.79-1.15), respectively (p > 0.05 for all
       comparisons; paired t test). A 20% difference in AUC0-infinity could be
       detected with 90% power. Also, there were no significant changes in
       laboratory values or electrocardiograms, or in rifabutin pharmacokinetic
       parameters when the two agents were coadministered. Based on the safety
       and pharmacokinetic assessments, rifabutin did not appear to interact
       with ddI.
 DE    Adult  Biological Availability  Didanosine/ADVERSE
       EFFECTS/*PHARMACOKINETICS/THERAPEUTIC USE  Drug Interactions  Drug
       Therapy, Combination  Female  Human  HIV Infections/DRUG
       THERAPY/*METABOLISM  Male  Middle Age  Rifabutin/ADVERSE
       EFFECTS/*PHARMACOKINETICS/THERAPEUTIC USE  Support, Non-U.S. Gov't
       CLINICAL TRIAL  CLINICAL TRIAL, PHASE I  JOURNAL ARTICLE

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