Phase I evaluation of zalcitabine administered to human immunodeficiency virus-infected children.
The safety, tolerability, and pharmacokinetics of zalcitabine (ddC) in a single oral dose (0.02 mg/kg) was evaluated in 23 mildly symptomatic human immunodeficiency virus-infected children (mean age, 4.2 years). After administration of ddC, blood samples were obtained at 0.5, 1, 1.5, 2, 4, 6, and 8 h for analysis. The drug was well tolerated and no side effects were noted. Plasma ddC levels were determined by ion spray liquid chromatography/tandem mass spectrometry. ddC was rapidly absorbed, with a mean maximum plasma concentration of 9.3 ng/mL (range, 3.2-14.1) attained within a mean of 1 h (range, 0.5-2.0). Mean elimination half-life was 1.4 h (range, 1.0-3.5), mean area under the plasma concentration-time curve was 25 ng.h/mL (range, 11-37), and mean total body clearance was 14.6 mL/min/kg (range, 8.9-30.6). Plasma concentrations were lower and the half-life shorter in these children than in adults given comparable doses, suggesting that ddC may be cleared more rapidly in children than adults.
Chadwick
E G
EG
Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois, USA.
Nazareno
L A
LA
Nieuwenhuis
T J
TJ
Massarella
J W
JW
de Dennis
S R
SR
Williams
K
K
Yogev
R
R
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006207:Half-Life; D006801:Humans; D007223:Infant; D008297:Male; D016047:Zalcitabine / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000998:Antiviral Agents; D016047:Zalcitabine