Table 4.
Rifapentine and rifampin pharmacokinetic/pharmacodynamic outcomes in liquid media
| Rifapentine pharmacokinetic/pharmacodynamic outcomesa | ||||
|---|---|---|---|---|
| Rifapentine AUC0‐24 a (μg × h/mL) | Aggregate cavity size on chest radiograph (cm) | Study site in Africa | Percent participants with negative cultures in liquid media at completion of intensive‐phase therapy, mean [95% CI] |
Time (d) calculated for 50% participants to develop stable conversion to negative cultures in liquid media while receiving antituberculosis treatment [range: 5%, 95% participants] |
| > 350 | < 4 | Yes | 67 [53, 83] | 45 [14, 88] |
| ≥ 4 | Yes | 40 [20, 56] | 66 [20, > 120] b | |
| < 4 | No | 79 [70, 87] | 39 [12, 76] | |
| ≥ 4 | No | 48 [30, 70] | 57 [17, 111] | |
| 325 | < 4 | Yes | 61 [44, 78] | 48 [15, 94] |
| ≥ 4 | Yes | 36 [20, 56] | 66 [20, > 120] c | |
| < 4 | No | 73 [65, 83] | 42 [13, 81] | |
| ≥ 4 | No | 48 [30, 70] | 57 [17, 111] | |
| < 300 | < 4 | Yes | 37 [27, 48] | 68 [21, > 120] c |
| ≥ 4 | Yes | 37 [25, 49] | 68 [21, > 120] c | |
| < 4 | No | 47 [28, 63] | 58 [18, 114] | |
| ≥ 4 | No | 44 [22, 72] | 58 [18, 114] | |
| Rifampin pharmacodynamic outcomesd | |||
|---|---|---|---|
| Extent of lung infiltrate on chest radiographd | Productive cough at baseline | Percent of participants with negative cultures in liquid media at completion of intensive‐phase therapy, mean [95% CI] | Time (d) calculated for 50% participants to develop negative cultures in liquid media while receiving antituberculosis treatment [range: 5%, 95%] |
| < 25% | Yes | 67 [55, 79] | 46 [16, 85] |
| No | 93 [72, 100] | 32 [11, 58] | |
| ≥ 25% | Yes | 37 [30, 45] | 66 [22, 122] |
| No | 68 [42, 92] | 45 [15, 84] | |
AUC0‐24 computed as rifapentine dose/CL, and the AUC0‐24 targets refer to daily drug administration 7 days/week. Estimates of rifapentine AUC95 and inspection of Figure 1 and Supplementary Figure S4 were used to formulate target rifapentine AUC0‐24 cutoffs of >350 and <300 μg × h/mL. Participants with Karnofsky score ≤90 are grouped by the significant covariates of rifapentine exposure, aggregate cavity size on chest radiograph, and geographic origin of study site. To more simply display the most relevant pharmacokinetic/pharmacodynamic data from most of the study participants, data for 38 participants with Karnofsky score of 100 are separately presented in Supplementary Table S4. Proportion of participants with estimated treatment time >120 days were 7.7% (b) and 8.8% (c). AUC0‐24, area under the concentration‐time curve from 0 to 24 h; AUC95, area under the concentration‐time curve to achieve stable conversion in 95% of participants; CI, confidence interval; CL, clearance.
dParticipants grouped by the significant covariates of percentage area of extent of lung infiltrate on chest radiograph and baseline cough with or without sputum production.