Table 1.
Patient demographic characteristics.
Table 2.
Population PK parameter estimates of PZA for the final model and bootstrap results.
Fig 1.
Goodness-of-fit plots of the final model.
(A) Observed versus population predicted concentrations. (B) Observed versus individual predicted concentrations. (C) Concentration weighted residuals versus population predicted population. (D) Individual weighted residuals versus individual predicted concentrations. Open purple circles represent the plasma concentrations of PZA, and solid dark blue lines represent locally weighted least-squares regression according to plasma concentration.
Fig 2.
Prediction-corrected visual predictive checks.
The black and red dots represent the observed PZA concentrations in Indonesian and Korean, respectively. The solid orange line represents the median predicted concentration. The shaded area represents the 90% prediction interval of the simulated PZA concentrations based on the final model.
Fig 3.
Relationships of DM and old DM with PK parameters of each ethnicity.
(A) Area under concentration of 0 to 24 hours between DM and non-DM patients in Indonesian ethnic. (B) Maximum concentration between DM and non-DM patients in Indonesian ethnic. (C) Apparent clearance between DM and non-DM patients in Indonesian ethnic. (D) Area under concentration of 0 to 24 hours between old DM and other patients in Korean ethnic. (E) Maximum concentration between old DM and other patients in Korean ethnic. (F) Apparent clearance between old DM and other patients in Korean ethnic. Box plot showing the interquartile range of each PK parameter. The groups are represented as follows: pink, DM in Indonesian, and old DM in Korean; blue, non-DM in Indonesian, and other patients in Korean. The straight line in the upper part of the box plot represents the t-test results. **** P < 0.001, ns: non-significant). DM: diabetes mellitus, old DM: ≥ 60 years old patients with DM, Other patients: patients who aged < 60 years old with or without DM, PZA: Pyrazinamide, PK: pharmacokinetics.
Fig 4.
Probability of achieving a target area under the concentration-time curve from 0 to 24 h (AUC0-24) of ≥ 363 mg.h/L for the simulated PZA dosing regimens according to the different ethnicities and DM status.
The WHO weight bands were represented by different colors line. Red line: < 40 kg weight band, blue line: 40-54 kg weight band, purple line: 55-70 kg weight band, and green line: > 70 kg weight band. The probability of target attainment (PTA) according to ethnicities is shown for (A) Indonesian; (B) Korean with each ethnic covariate of DM characteristics. DM: diabetes melltus, PZA: Pyrazinamide, Other patients: patients who aged < 60 years old with or without DM.
Fig 5.
Probability of achieving maximum concentration (Cmax) of >60 mg/L for the simulated PZA dosing regimens according to the ethnicities and DM characteristics.
The WHO weight bands were represented by different colors line. Red line: < 40 kg weight band, blue line: 40-54 kg weight band, purple line: 55-70 kg weight band, and green line: > 70 kg weight band. The probability of target attainment (PTA) according to ethnicities is shown for (A) Indonesian; (B) Korean with each ethnic covariate of DM characteristics. DM: diabetes melltus, PZA: Pyrazinamide, Other patients: patients who aged < 60 years old with or without DM.