Table 6.
Overview of pharmacokinetic parameters of pretomanid evaluated in various animal studies
| Reference | Animal model | Infected | Dose (mg/kg) | Treatment combination | Treatment duration | Route of drug administration | Sample | Methods | Pretomanid Tmax (h) | T½ (h) | C max (mg/L) | AUC time span | AUC (μg·h/mL) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Lakshminarayana et al. (2014)105 | Mice, CD-1 | No | 25 | No | Oral | Plasma | LC-MS/MS | 2 | 2.7 | 6 | 0–24 | 50.9 | |
| 10 | No | Intravenous | Plasma | LC-MS/MS | 1.6 | ||||||||
| Nuermberger et al. (2006)108 | Mice, BALB/c | Yes | 100 | No | Single dose | Oral gavage | Serum | HPLC | 4.7 | 12.8 | 21.4 | 0–24 | 327.6 |
| Mice, BALB/c | Yes | 100 | No | 2 months | Oral gavage | Serum | HPLC | 1.3 | 18.3 | 25 | 0–24 | 396.8 | |
| Mice, BALB/c | Yes | 100 | RIF (10) + INH (25) + PZA (150) | Single dose | Oral gavage | Serum | HPLC | 11.0 | 11.3 | 20.4 | 0–24 | 370.5 | |
| Mice, BALB/c | Yes | 100 | RIF (10) + INH (25) + PZA (150) | 2 months | Oral gavage | Serum | HPLC | 3.3 | 9.7 | 27.7 | 0–24 | 424 | |
| Tasneen et al. (2008)106 | Mice, BALB/c | 54 | Single dose | Oral | Serum | 15.1 | 0–∞ | 127.5 | |||||
| Ahmad et al. (2011)110 | Mice, BALB/c | No | 3–1458 | Single drug | Single dose | Esophagal gavage | Serum | HPLC | 4 | 4–6 | |||
| Mudde et al. (2021)107 | Mice, BALB/c | Yes | 100 | BDQ (25) + MXF (100) + PZA (150) | 4 weeks | Oral | Serum | LC-MS/MS | 6.89–7.03 | 0–24 | 104.2 | ||
| Mice, BALB/c | Yes | 100 | BDQ (25) + LZD (100) | 4 weeks | Oral | Serum | LC-MS/MS | 7.70–9.50 | 0–24 | 99.13 | |||
| Wang et al. (2018)101 | Rats, Sprague-Dawley | No | 20 | Single drug | Single dose | Oral | Plasma | LC-MS/MS | 5 | 5.6 | 3.87 | 0–36 | 2678.74 |
| 0–∞ | 2787.23 | ||||||||||||
| Wang et al. (2015)96 | Rats, Sprague-Dawley | No | 20 | Single drug | Single dose | Oral | Plasma | LC-MS/MS | 6 | 8.3 | 3.48 | 0–36 | 3291.9 |
| 0–∞ | 3552.7 | ||||||||||||
| Rats, Sprague-Dawley | No | 40 | Single drug | Single dose | Oral | Plasma | LC-MS/MS | 6 | 6.2 | 7.98 | 0–36 0–∞ |
5850.9 6007.9 |
|
| Rats, Sprague-Dawley | No | 80 | Single drug | Single dose | Oral | Plasma | LC-MS/MS | 6 | 7.4 | 15.29 | 0–36 | 12445.1 | |
| 0–∞ | 13072.1 | ||||||||||||
| Bratkowska et al. (2015)99 | Rats, Sprague Dawley | No | 20 | Single drug | Oral | Plasma | LC-MS/MS | 6 | 0.63 | 0–∞ | 3.7248 | ||
| Rats, Sprague Dawley | No | 20 | Single drug | Intraperitoneal | Plasma | LC-MS/MS | 0.25 | 1.15 | 0–∞ | 3.9885 | |||
| Wang et al. (2014)100 | Rats, Sprague-Dawley | 20 | Single drug | Single dose | Oral | Plasma | LC-MS/MS | 6 | 3.485 | 0–36 | 3297.503 | ||
| 0–∞ | 3558.315 | ||||||||||||
| Rats, Sprague-Dawley | 20 | MXF (40) + PZA (160) | Single dose | Oral | Plasma | LC-MS/MS | 4.6 | 6.388 | 0–36 | 4851.288 | |||
| 0–∞ | 5052.658 | ||||||||||||
| Sung et al. (2009)136 | Guinea pigs | No | 20 | Intravenous | Plasma | HPLC | 0.11 | 1.91 | 9.19 | 0–24 | 26.54 | ||
| Guinea pigs | No | 40 | Oral gavage | Plasma | HPLC | 4.00 | 2.43 | 4.14 | 0–24 | 25.77 | |||
| Guinea pigs | No | 20 | Insufflation | Plasma | HPLC | 4.33 | 2.83 | 2.01 | 0–24 | 14.80 | |||
| Guinea pigs | No | 40 | Insufflation | Plasma | HPLC | 3.25 | 4.38 | 3.42 | 0–24 | 32.34 | |||
| Guinea pigs | No | 60 | Insufflation | Plasma | HPLC | 3.60 | 5.91 | 4.58 | 0–32 | 50.96 | |||
| Dutta et al. (2013)109 | Guinea pigs | No | 12.5 | Single drug | Single dose | Oral | Serum | HPLC | 2.65 | 1.94 | 1.68 | 0–∞ | 11.19 |
| Guinea pigs | No | 25 (BID) | Single drug | 7 days | Oral | Serum | HPLC | 2.25 | 4.7 | 2.99 | 0–∞ | 42.19 | |
| Guinea pigs | No | 50 | Single drug | Single dose | Oral | Serum | HPLC | 2.66 | 3.16 | 5.84 | 0–∞ | 39.79 | |
| Guinea pigs | No | 50 (BID) | Single drug | 7 days | Oral | Serum | HPLC | 7 | 2.16 | 5.79 | 0–∞ | 70.95 |
T max, time until the highest concentration is reached; T½, half-life time, time until the initial drug concentration is halved; Cmax, highest concentration reached; BID, bis in die, i.e. twice a day.