Multivariate linear regression analysis of factors associated with AUC0–24, C max and CSF concentrations of isoniazid, rifampicin and pyrazinamide in Indonesian children treated for TBM
| AUC0–24, hour∙mg/L (B (95% CI)) |
C
max, mg/L (B (95% CI)) |
C
CSF0–8, mg/L (B (95% CI)) | |
| Isoniazid | |||
| Age, years | n/a | −0.020 (−0.043 to 0.003)# | n/a |
| Random blood glucose, mg/dL | −0.002 (−0.006 to 0.003) | −0.004 (−0.009 to 0.001) | −0.007 (−0.015 to 0.001)# |
| Drug dose, mg/kg | 0.016 (−0.048 to 0.080) | n/a | 0.046 (−0.058 to 0.151) |
| Drug administration via NGT, no/yes | 0.439 (0.143 to 0.735)** | 0.130 (−0.160 to 0.420) | 0.289 (−0.197 to 0.775) |
| Rifampicin | |||
| Age, years | −0.009 (−0.028 to 0.010) | −0.008 (−0.029 to 0.012) | −0.021 (−0.052 to 0.009) |
| Random blood glucose, mg/dL | −0.003 (−0.007 to 0.001) | −0.005 (−0.009 to −0.0003)* | n/a |
| Drug dose, mg/kg | 0.014 (−0.021 to 0.048) | n/a | 0.030 (−0.030 to 0.091) |
| Drug administration via NGT, no/yes | n/a | 0.067 (−0.194 to 0.328) | 0.019 (−0.365 to 0.403) |
| Pyrazinamide | |||
| Random blood glucose, mg/dL | −0.006 (−0.010 to −0.003)** | −0.003 (−0.005 to −0.001)** | −0.006 (−0.010 to −0.003)** |
| Drug dose, mg/kg | 0.010 (−0.006 to 0.027) | 0.010 (0.001 to 0.020)* | 0.010 (−0.006 to 0.027) |
| Drug administration via NGT, no/yes | −0.068 (−0.293 to 0.156) | 0.036 (−0.095 to 0.167) | −0.068 (−0.293 to 0.156) |
Data are presented as regression coefficients (B) and 95% CIs. #p<0.1, *p<0.05, **p<0.01.
The total explained variance (R2) for isoniazid AUC0–24: 0.57, isoniazid C max: 0.46, isoniazid C CSF0–8: 0.45; rifampicin AUC0–24: 0.31, rifampicin C max: 0.38, rifampicin C CSF0–8: 0.33, pyrazinamide AUC0–24: 0.53, pyrazinamide C max: 0.63 and pyrazinamide C CSF0–8: 0.53.
AUC0–24, area under the plasma concentration–time curve from 0 to 24 hours postdose at the first PK assessment; C CSF0–8, CSF concentrations during 0–8 hours postdose at the first PK assessment; CI, confidence interval; C max, peak plasma concentration at the first PK assessment; n/a, non-applicable; NGT, nasogastric tube; TBM, tuberculous meningitis.