TABLE 1.
Parameters of pyrazinamide, pyrazinoic acid, and 5-hydroxypryazinamide in adult TB/HIV-coinfected patients estimated by the final population pharmacokinetic modela
| Parameter | Mean (% RSE) | 95% confidence interval |
|---|---|---|
| PZA CL/F (liters/h) | 4.7 (8.12) | 4.08 to 5.5 |
| PZA V/F (liter) | 62.0 (7.47) | 53.7 to 72.2 |
| Ka (h−1) | 3.5 (233) | 2.01 to 9.6 |
| F | 1 FIX | |
| POA CL/F (liters/h) | 9.5 (9.52) | 7.72 to 11.2 |
| F POA | 0.45 (4.75) | 0.41 to 0.488 |
| OHPZA CL/F (liters/h) | 15.8 (8.25) | 13.7 to 19.2 |
| Effect of female sex on F | 0.47 (27.8) | 0.244 to 0.755 |
| Effect of serum creatinine on POA CL/F | −0.0064 (28.7) | −0.00264 to −0.0104 |
| Effect of study arm on PZA, POA and OHPZA V/F | −0.24 (27.1) | −0.091 to −0.385 |
| PZA proportional error | 0.32 (6.01) | 0.281 to 0.36 |
| POA proportional error | 0.3 (7.38) | 0.261 to 0.347 |
| OHPZA proportional error | 0.278 (8.96) | 0.23 to 0.327 |
| PZA additive error | 0.001 FIX | |
| POA additive error | 0.001 FIX | |
| POA additive error | 0.001 FIX | |
| IIV CL/F (%) | 40.5 (18.3) | 28.8 to 41.2 |
| IIV Ka (%) | 351.1 (51.5) | 116.2 to 216.1 |
| IIV F (%) | 38.0 (17.4) | 31.4 to 44.0 |
| IIV POA CL/F (%) | 33.9 (52.1) | 10.1 to 41.6 |
| IIV FPOA (%) | 27.4 (20.3) | 21.6 to 31.1 |
| IIV OHPZA CL/F (%) | 16.1 (59.3) | 5.3 to 30.9 |
a
RSE, relative standard error; PZA, pyrazinamide; POA, pyrazinoic acid; OHPZA, 5-hydroxypyrazinamide; CL/F, oral clearance; V/F, oral volume of distribution; Ka, absorption constant; F, bioavailability; FPOA, fraction of pyrazinamide forming pyrazinoic acid; IIV, interindividual variability; FIX, parameter fixed to the indicated value.