Phosphorylated zidovudine concentrations in mononuclear cells in pediatric patients with human immunodeficiency virus infections. NLM AIDSLINE Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

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Phosphorylated zidovudine concentrations in mononuclear cells in pediatric patients with human immunodeficiency virus infections.

Pediatr AIDS HIV Infect. 1997 Apr;8(2):120-6. Unique Identifier : AIDSLINE MED/97323598
Wintermeyer SM; Nahata MC; Brady MT; Sobol BJ; Venglarcik JS 3rd; Baker RC; Hunkler JA; McOwen NM; Children's Medical Center of Northwest Ohio, Toledo, USA.

Abstract: PURPOSE: The efficacy of zidovudine (ZDV) in patients with HIV-1 infection may decrease over time due to its decreased activation. The objectives of this study were to determine ZDV concentrations in plasma, active phosphorylated zidovudine (pZDV) concentrations in mononuclear cells, and assess the markers of immune function and drug toxicity during extended therapy. METHODS: Pediatric patients (aged 3 months to 18 years) with HIV-1-infection were enrolled in the study. For each patient, one blood sample was collected at each of eight routine visits to measure plasma ZDV and ZDV concentrations by a radioimmunoassay. Data including demographic information, immunological markers (CD2+, CD3+, CD4+, CD5+/19+, CD8+, CD16+, CD19+, CD38+/8+ lymphocytes), hematologic function (absolute neutrophil count, white blood cell with differential, hemoglobin, and red blood cell count), concurrent medications, and dosage regimens were obtained. RESULTS: The data from 13 patients were as follows: age: 2-18 years; range of ZDV dose: 76-238 mg/m2, total ZDV daily dosage: 264-720 mg/m2; duration of ZDV therapy prior to study: 1 to 37 months; time in study: 180-394 days; plasma ZDV concentration range: 5-1021 ng/ml; and pZDV concentration range: 0-5.382 pmol/10(6) cells. Both plasma ZDV and intracellular pZDV concentrations had a marked inter- and intrapatient variability. The pZDV concentrations decreased significantly over time in one pediatric patient (p < 0.05), tended to decrease but not significantly in three patients, and no decrease was detected in nine patients due to high variability. In our population, neither immunological nor drug toxicity markers changed over time. CONCLUSIONS: Marked inter- and intrapatient variability in pZDV concentrations was observed. The ability to phosphorylate ZDV, however, did not appear to change significantly in 12 of 13 pediatric patients with HIV-1 infection during the study period of 6-13 months.
Keywords: *Anti-HIV Agents/PHARMACOKINETICS *HIV Infections/DRUG THERAPY *Monocytes/METABOLISM *Thymine Nucleotides/PHARMACOKINETICS *Zidovudine/ANALOGS & DERIVATIVESKWDanti-hivagents/pharmacokineticsKWDhivinfections/drugtherapyKWDmonocytes/metabolismKWDthyminenucleotides/pharmacokineticsKWDzidovudine/analogs&derivatives
971030
M97A1314

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