       Document 0275
 DOCN  M95B0275
 TI    A phase I/II evaluation of stavudine (d4T) in children with human
       immunodeficiency virus infection.
 DT    9511
 AU    Kline MW; Dunkle LM; Church JA; Goldsmith JC; Harris AT; Federici ME;
       Schultze ME; Woods L; Loewen DF; Kaul S; et al; Department of
       Pediatrics, Baylor College of Medicine, Houston, TX; 77030, USA.
 SO    Pediatrics. 1995 Aug;96(2 Pt 1):247-52. Unique Identifier : AIDSLINE
       MED/95357106
 AB    OBJECTIVES. To determine the pharmacokinetic properties, tolerance,
       safety, and preliminary activity of stavudine in human immunodeficiency
       virus (HIV)-infected children. DESIGN. Phase I/II, open and dose-ranging
       (0.125 to 4 mg/kg/day in two divided doses). PATIENTS. Thirty-seven
       HIV-infected children (median age, 5.5 years; range, 7 months to 15
       years) with a median CD4+ lymphocyte count at baseline of 242
       cells/microL (range 2 to 2290 cells/microL). Thirty children had
       symptomatic HIV disease at entry; seven had HIV-related
       immunosuppression alone. Twenty-nine subjects had a history of prior
       zidovudine (ZDV) therapy. RESULTS. As compared with adults receiving the
       same weight-adjusted doses, the children we studied had lower maximum
       observed stavudine plasma concentrations (CMAX) and area under the
       plasma concentration versus time curves (AUC), and more rapid stavudine
       elimination. The absolute oral bioavailability of the drug ranged from
       61% to 78%. There was no plasma accumulation of the drug between day 1
       and week 12. Week 12 cerebrospinal fluid stavudine concentrations in
       seven subjects, obtained approximately 2 to 3 hours after oral doses,
       ranged from 16% to 97% of concomitant plasma concentrations. Stavudine
       was well-tolerated and there were no dose-related clinical or laboratory
       adverse events. One subject with baseline neurologic abnormalities
       experienced a transient episode of apparent pain or discomfort in her
       fingers, possibly related to stavudine. All other adverse events were
       attributed to underlying disease. Stavudine activity, measured
       indirectly by CD4+ lymphocyte count and serum p24 antigen concentration
       changes, was observed in some subjects. Progression of HIV disease and
       survival correlated with prior ZDV therapy, HIV disease classification,
       baseline CD4+ lymphocyte count, and weight growth velocity. CONCLUSIONS.
       Stavudine appears to hold promise for the treatment of HIV infection in
       children. Its pharmacokinetic properties are consistent and predictable,
       and it appears to be remarkably well-tolerated and safe. Although our
       study was not designed to assess the drug's efficacy, preliminary
       clinical and laboratory evidence of activity was observed.
 DE    Administration, Oral  Adolescence  Adult  Biological Availability  Body
       Weight  Child  Child, Preschool  Comparative Study  CD4 Lymphocyte
       Count/DRUG EFFECTS  Disease Progression  Female  Growth  Human  HIV Core
       Protein p24/BLOOD  HIV Infections/CLASSIFICATION/*DRUG THERAPY  Infant
       Male  Stavudine/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/BLOOD/
       PHARMACOKINETICS/*THERAPEUTIC USE  Support, Non-U.S. Gov't  Support,
       U.S. Gov't, P.H.S.  Survival Rate  Zidovudine/ADMINISTRATION &
       DOSAGE/THERAPEUTIC USE  CLINICAL TRIAL  CLINICAL TRIAL, PHASE I
       CLINICAL TRIAL, PHASE II  JOURNAL ARTICLE

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

