RELATIONSHIP BETWEEN DIDANOSINE EXPOSURE AND SURROGATE MARKER RESPONSE IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED OUTPATIENTS

We used information available from routine clinic visits to characteri ze the pharmacokinetics of didanosine in 82 human immunodeficiency vir us-infected patients. A total of 271 blood samples were collected for the measurement of didanosine concentrations in plasma (mean +/- stand ard deviation [SD], 3.30 +/- 2.21 samples/patient). Bayesian estimates of didanosine oral clearance (CLoral) were obtained for these patient s by the POSTHOC option within the NONMEM software package. Population priors from a previous NONMEM analysis of didanosine pharmacokinetics were used. The mean +/- SD CLoral was 132 +/- 27.7 liters/h, which ag rees reasonably well with estimates obtained from previous pharmacokin etic studies of didanosine. Estimates of individual didanosine exposur e were then used to consider potential relationships between drug expo sure and surrogate marker response over a 6-month period. No correlati ons were found between the didanosine area under the concentration tim e curve from 0 to 6 months and the absolute CD4 cell count (r = 0.305; 0.1 < P < 0.2), weight response (r = 0.0857; P > 0.4), or percentage of CD4 lymphocytes (r = 0.0559; P > 0.4). Future efforts to characteri ze didanosine exposure in outpatients by random sampling methods shoul d involve more directed efforts to limit residual variability in the d ata.