Document 0490
 DOCN  M9490490
 TI    Pharmacokinetics of zidovudine and dideoxyinosine alone and in
       combination in patients with the acquired immunodeficiency syndrome.
 DT    9411
 AU    Barry M; Howe JL; Ormesher S; Back DJ; Breckenridge AM; Bergin C;
       Mulcahy F; Beeching N; Nye F; Department of Pharmacology and
       Therapeutics, University of; Liverpool.
 SO    Br J Clin Pharmacol. 1994 May;37(5):421-6. Unique Identifier : AIDSLINE
       MED/94331278
 AB    1. Zidovudine (ZDV) has proved unsuccessful in controlling disease
       progression over extended periods of time in patients with AIDS.
       Combination of ZDV with another reverse transcriptase inhibitor,
       dideoxyinosine (ddI) may improve the duration of effectiveness of
       antiretroviral therapy. The aim of this study was to investigate the
       possibility of a pharmacokinetic drug interaction between ZDV and ddI.
       2. The pharmacokinetics of ZDV and ddI were determined in eight patients
       with AIDS who were randomised to receive ZDV 250 mg orally, ddI 250 mg
       orally or a combination of ZDV 250 mg plus ddI 250 mg orally on 3 study
       days separated by 1 week. 3. The administration of ZDV did not
       significantly alter ddI pharmacokinetics. The mean AUC was 6.8 +/- 2.0
       s.d. and 7.6 +/- 2.5 s.d. mumol l-1 h and oral clearance was 2766 +/-
       686 and 2660 +/- 1297 ml min-1 in the presence and absence of ZDV,
       respectively. 4. In the presence of ddI the elimination half-life of ZDV
       was increased significantly by 18% from 1.1 +/- 0.3 to 1.3 +/- 0.3 h (P
       < 0.05) and the mean AUC increased significantly by 35% from 4.8 +/- 1.5
       to 6.5 +/- 1.5 mumol l-1 h (P < 0.05). The clearance was decreased by
       29% from 3518 +/- 1123 to 2505 +/- 575 ml min-1, but this difference was
       not significant. The renal clearance of ZDV was not altered by ddI. 5.
       Administration of ddI also resulted in a significant 22% increase in the
       AUC of GZDV, from 28.5 +/- 15.7 to 34.9 +/- 12.8 mumol l-1 h (P <
       0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 DE    Acquired Immunodeficiency Syndrome/*DRUG THERAPY/METABOLISM
       Administration, Oral  Adult  Chromatography, High Pressure Liquid
       Didanosine/ADMINISTRATION & DOSAGE/*PHARMACOKINETICS/THERAPEUTIC  USE
       Drug Interactions  Drug Therapy, Combination  Half-Life  Human  Male
       Metabolic Clearance Rate  Middle Age  Support, Non-U.S. Gov't
       Zidovudine/ANALOGS & DERIVATIVES/ADMINISTRATION & DOSAGE/BLOOD/
       *PHARMACOKINETICS/THERAPEUTIC USE/URINE  CLINICAL TRIAL  JOURNAL ARTICLE
       RANDOMIZED CONTROLLED TRIAL

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