Parameter estimates of isoniazid pharmacokinetics in TB-HIV-coinfected patients

DescriptiondEstimated valueRelative SE (%)
CLa (liters/h) (reference group, NAT2 rs1799930 GG)22.88
    Effect of NAT2 rs1799930 GA on CL (%)−26.336
    Effect of NAT2 rs1799930 AA on CL (%)−74.628
    Effect of efavirenz on CL (%)+24.127
Vca (liters)64.17
Kaa (reference formulations, RHZE, HR1, and HR2) (liters/h)1.7313
    Effect of formulation HR3 on Ka (%)95.128
Tlag (liters/h)0.25 (fixed)
F (reference formulation, RHZE)1 (fixed)
    Effect of formulation HR1 on F (%)+26.930
    Effect of formulation HR2 on F (%)−15.249
    Effect of formulation HR3 on F (%)+19.323
Vpa,b (liters)46.352
Proportional error (%)30.65
Additive error (mg/liter)0.17224
Between-subject variability of CLc (%CV)53.77
Between-subject variability of Vc (%CV)33.816
Between-occasion variability of Kac (%CV)73.112
Between-occasion variability of Fc (%CV)31.85
Between-occasion variability of Tlagc (%CV)9.56
  • a Allometric scaling was used for CL, Vc, Q, and Vp, and values are reported for an adult with a weight of 52 kg.

  • b Q and Vp were estimated using Bayesian priors, with typical values of 16.1 liters/h and 16.5 liters, respectively, from a previous study (7), with 50% uncertainty.

  • c The between-subject and between-occasion variability were assumed to be log-normally distributed and are reported as approximate coefficients of variation (%CV).

  • d NAT2, N-acetyltransferase 2; Ka, absorption rate constant; HR, isoniazid and rifampin fixed-dose combination; RHZE, isoniazid, rifampin, ethambutol, and pyrazinamide fixed-dose combination.