Parameter estimates of the final model for stavudine triphosphate in HIV-infected adults and children

ParameteraAdult (%RSEb) (n = 24)Child (n = 23)
CL (1012 cells/h)454 (9)230
Vc (1012 cells)2,569 (18)1,037
Q (1012 cells/h)469 (30)238
Vp (1012 cells)7,500 (58)3,027
ka (1/h)1.17c (46)
F1 (fixed)
Additive error (fmol/106 cells)0.6 (fixed)d
Proportional error (%)27.4 (8)
IIV CL (%CV)30.4 (21)
IOV F (%CV)36.2 (20)
IOV ka (%CV)30.6 (61)
  • a All clearance and volume of distribution parameters were estimated by allometric scaling using fat-free mass, and the typical values reported here refer to an adult with a median fat-free mass of 47.2 kg. The children values are also reported here for comparison, but they were not estimated separately in the model; they were just obtained by rescaling the adult values to the median fat-free mass of our children cohort, 19.1 kg. IIV and IOV were assumed to be log-normally distributed, and their magnitudes are reported here as approximate coefficient of variation (%CV). CL, apparent oral clearance; Vc, apparent central volume of distribution; Q, apparent oral intercompartmental clearance; Vp, apparent peripheral volume of distribution; ka, appearance rate constant; F, bioavailability, IIV, interindividual variability; IOV, interoccasion variability.

  • b RSE, relative standard error.

  • c A Bayesian prior with values from Horton et al. (18) was used for the estimation of ka.

  • d The estimate of the additive error was small and not stable, so it was fixed to 20% of the median LLOQ.