Document 0504
 DOCN  M9490504
 TI    Effect of dipyridamole on zidovudine pharmacokinetics and short-term
       tolerance in asymptomatic human immunodeficiency virus-infected
       subjects.
 DT    9411
 AU    Hendrix CW; Flexner C; Szebeni J; Kuwahara S; Pennypacker S; Weinstein
       JN; Lietman PS; Department of Infectious Diseases, Wilford Hall Medical
       Center,; Lackland AFB, Texas 78236-5300.
 SO    Antimicrob Agents Chemother. 1994 May;38(5):1036-40. Unique Identifier :
       AIDSLINE MED/94346802
 AB    Zidovudine delays the progression of infection and prolongs the survival
       of human immunodeficiency virus (HIV)-infected patients, but these
       benefits are limited by dose-related toxicity and the cost of the drug.
       Dipyridamole, in micromolar concentrations, acts synergistically with
       zidovudine, reducing the anti-HIV 95% inhibitory concentration of
       zidovudine 5- to 10-fold in vitro. We sought to establish a
       well-tolerated dose of dipyridamole for use in combination with
       zidovudine and to detect clinically significant pharmacokinetic
       interactions. Both objectives are essential for planning studies of the
       efficacy of the zidovudine-dipyridamole combination. Eleven asymptomatic
       HIV-infected subjects (median CD4+ cell count, 311 cells per mm3), 10 of
       whom had been on zidovudine at 500 mg/day for at least 6 months, were
       admitted to the study. Zidovudine pharmacokinetics were measured on day
       1. Dipyridamole was then begun at 600 mg/day (subjects 1 to 3) or 450
       mg/day (subjects 4 to 11), and zidovudine and dipyridamole
       pharmacokinetics were measured on day 5. All subjects given 600 mg of
       dipyridamole per day developed headache or nausea, or both. Six of eight
       subjects given dipyridamole at 450 mg/day developed headache or mild
       nausea that resolved after a median of 2 days. The area under the
       zidovudine concentration-time curve was not significantly different on
       day 1 in comparison with that on day 5 (P = 0.11). Symptoms were
       significantly correlated with the maximum zidovudine concentrations,
       which were achieved when dipyridamole was dosed concomitantly (p =
       0.03). Total (free and protein-bound) dipyridamole trough concentrations
       were near those demonstrating synergy with zidovudine against HIV in
       vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
 DE    Adult  Dipyridamole/ADVERSE EFFECTS/BLOOD/*PHARMACOLOGY  Drug
       Combinations  Drug Interactions  Human  HIV
       Seropositivity/COMPLICATIONS/*METABOLISM  Iodine
       Radioisotopes/DIAGNOSTIC USE  Male  Orosomucoid/METABOLISM  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Zidovudine/*ADVERSE
       EFFECTS/*PHARMACOKINETICS  JOURNAL ARTICLE

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