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Clinical Pharmacology of 2′,3′-Dideoxyinosine in Human Immunodeficiency Virus-Infected Children
Frank M. Balis, Philip A. Pizzo, Karina M. Butler, Mary E. Hawkins, Pirn Brouwers, Robert N. Husson, Freda Jacobsen, Susan M. Blaney, Janet Gress, Paul Jarosinski and David G. Poplack
The Journal of Infectious Diseases
Vol. 165, No. 1 (Jan., 1992), pp. 99-104
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/30112498
Page Count: 6
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The pharmacokinetics of intravenous and oral 2′,3′-dideoxyinosine (ddl) and the relationships between pharmacokinetic parameters and measures of response were studied in 48 human immunodeficiency virus-infected children. Disappearance of ddl 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/m³. After oral administration, ddl absorption was limited and variable (mean bioavailability, 19% ± 17%). A plasma ddl 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 ddl 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.
The Journal of Infectious Diseases © 1992 Oxford University Press