LIMITED SAMPLING MODELS FOR THE ANTIRETROVIRAL AGENT DIDANOSINE

Limited sampling strategies for the antiretroviral agent didanosine (d dI) have been studied in order to estimate the area under the plasma c oncentration-time curve (AUG) and the maximum plasma concentrations (C -max). Thirteen different models have been investigated in a test data set of 22 curves from 15 HIV-infected adults. These models were subse quently validated using 23 curves from another 15 HIV-infected adults. A 2-time-point model, consisting of the ddI concentration at t = 0.75 h (C-0.75) and t= 4 h (C-4) after intake of the drug appeared to be t he best model for predicting AUC values. C,,, values were best predict ed by a model consisting of only one sample at t = 0.75 h after ingest ion of the drug. The equations for the limited sampling models are: AU C(h.mg/l) = .25(h.mg/l)+1.16(h).C-0.75(mg/l)+5.43(h).C-4(mg/l) and C-m ax(mg/l)=0.15(mg/l)+1.00.C-0.75(mg/l) The limited sampling model for t he estimation of AUC values of ddI gave better predictions than previo usly developed models in HIV-infected children.