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A limited sampling strategy (LSS) to estimate the exposure to isoniazid was developed considering N-acetyltransferase 2 (NAT2) genotypes in Korean patients with tuberculosis. The influence of the genotypes on the pharmacokinetics of isoniazid was also evaluated. A total of 33 participants participated in the study and received isoniazid 300 mg once daily. Evaluable participants consist of ten slow (SA), fourteen intermediate (IA) and six rapid acetylators (RA). As expected, isoniazid exposure was higher (mean AUC, 28.4 versus 7.6 mg*h/L) and systemic clearance lower (mean apparent clearance, 14.8 versus 50.6 L/h) in SAs than RAs. The formulas to estimate isoniazid exposure were constructed using one or more concentration-time points that correlate with the area under the concentration-time curve (AUC). The LSS using a formula of single concentration-time point at 4 h post dose (C 4 ) is applicable for all acetylators to the therapeutic drug monitoring (TDM) of isoniazid in patients with tuberculosis when evaluated using the Deming regression and Bland-Altman plot (AUC = 1.53 + 10.03*C 4 , adjusted r 2  = 0.95, p < 0.001). Considering that SAs are more prone to adverse effects, pre-dose NAT2 genotyping would be valuable for optimal isoniazid dosing in conjunction with TDM., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Diabetes mellitus (DM) is a well-known risk factor to develop tuberculosis (TB). Some reports indicate the serum concentrations of anti-TB drugs are lower in patients with TB and DM than those with TB only. Therefore, we developed a nonlinear mixed-effects model (NONMEM) to determine the population PK parameters of rifampin and assessed the effects of DM status in patients with TB. One-compartment linear modeling with first-order absorption was evaluated using the 206 plasma samples of rifampin from 54 patients with DM. Based on the final model, DM affected the absorption rate constant (ka) and the volume of distribution (Vd) of rifampin. The body mass index (BMI) of the patients affected rifampin clearance (CL). The ka of rifampin in patients with TB and DM was greater than that in patients with TB only. Further, the predicted Vd in patients with DM was greater than that in patients without DM. As Vd is inversely correlated with plasma concentrations, the rifampin concentrations were predicted to be lower in the patients with DM. The authors recommend administering the greater doses of rifampin for the treatment of TB in patients with DM compared with the doses for the patients without DM to prevent treatment failure., (Copyright © 2014 Elsevier Ltd. All rights reserved.)