Document 0113
 DOCN  M9480113
 TI    Pharmacokinetic evaluation of the combination of zidovudine and
       didanosine in children with human immunodeficiency virus infection.
 DT    9410
 AU    Mueller BU; Pizzo PA; Farley M; Husson RN; Goldsmith J; Kovacs A; Woods
       L; Ono J; Church JA; Brouwers P; et al; Pediatric Branch, National
       Cancer Institute, National Institutes; of Health, Bethesda, MD 20892.
 SO    J Pediatr. 1994 Jul;125(1):142-6. Unique Identifier : AIDSLINE
       MED/94293107
 AB    As part of a phase I/II trial in children infected with human
       immunodeficiency virus, we studied the pharmacokinetics of zidovudine
       and didanosine administered as single agents and in combination.
       Zidovudine (60 to 180 mg/m2 per dose) was given orally every 6 hours,
       and didanosine (60 to 180 mg/m2 per dose) every 12 hours.
       Pharmacokinetic samples were obtained from 54 patients and the area
       under the plasma concentration-time curve (AUC) was estimated by means
       of a previously defined limited sampling strategy. Follow-up blood
       samples were obtained after 4 and 12 weeks of treatment. The mean AUC
       for zidovudine ranged from 4.8 mumol.hr per liter at 60 mg/m2 to 11.0
       mumol.hr per liter at the 180 mg/m2 level, and increased in proportion
       to the dose. The mean AUC for didanosine ranged from 2.8 mumol.hr per
       liter (60 mg/m2) to 8.0 mumol.hr per liter (180 mg/m2), with a wide
       interpatient variability. The AUCs of zidovudine and didanosine remained
       unchanged when the agents were administered in combination. There was no
       significant change in the AUCs of either drug after 4 and 12 weeks in
       comparison with those on day 3 of therapy. However, there was greater
       interpatient and intrapatient variability with didanosine than with
       zidovudine. These observations have implications for the future utility
       of therapeutic drug monitoring with these agents.
 DE    Adolescence  Adult  Child  Child, Preschool  Didanosine/ADMINISTRATION &
       DOSAGE/*PHARMACOKINETICS/THERAPEUTIC  USE  Dose-Response Relationship,
       Drug  Drug Interactions  Drug Monitoring  Drug Therapy, Combination
       Female  Human  HIV Infections/BLOOD/*DRUG THERAPY  Infant  Male
       Zidovudine/ADMINISTRATION & DOSAGE/*PHARMACOKINETICS/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).