Clinical pharmacology of 2',3'-dideoxyinosine in human immunodeficiency virus-infected children.
The pharmacokinetics of intravenous and oral 2',3'-dideoxyinosine (ddI) and the relationships between pharmacokinetic parameters and measures of response were studied in 48 human immunodeficiency virus-infected children. Disappearance of ddI from plasma after the intravenous dose was rapid and biexponential, with half-lives of 12 min and 1.0 h and a total clearance of 510 +/- 180 ml/min/m2. After oral administration, ddI absorption was limited and variable (mean bioavailability, 19% +/- 17%). A plasma ddI concentration-response relationship was observed for both decline in viral p24 antigen levels and improvement in intelligence quotient score. A limited sampling model was developed that accurately predicts the area under the ddI plasma concentration-time curve from one to three plasma samples. Although this pharmacokinetic study was done in children, the results also have relevance to adults and suggest that individualization of dose and schedule through therapeutic drug monitoring may be necessary to achieve optimal response.
Balis
F M
FM
Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Pizzo
P A
PA
Butler
K M
KM
Hawkins
M E
ME
Brouwers
P
P
Husson
R N
RN
Jacobsen
F
F
Blaney
S M
SM
Gress
J
J
Jarosinski
P
P
D000042:Absorption; D000284:Administration, Oral; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016049:Didanosine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004341:Drug Evaluation; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male
D016049:Didanosine