Table 4.
Pharmacokinetic parameters in rat following parenteral administration.
| Analyte | Bedaquiline |
|||
|---|---|---|---|---|
| In situ gel Formulation 1 | In situ gel Formulation 2 | PEG400 solution Formulation 5 | ||
| Dosing route | IM | IM | IM | IV |
| Dose (mg/kg) | 6 | 6 | 3 | 5 |
| n | 5a | 5a | 3b | 3c |
| C0 (ng/mL)d | – | – | – | 3589 (1779) |
| Cmax (ng/mL)d | 237 (34) | 410 (42) | 94.7 (12.5) | – |
| tmax (h)e | 6 (6–8) | 6 (4–6) | 6 (6–6) | – |
| tlast (h) | 672 | 672 | 80 | 80 |
| AUClast (ng.h/mL)d | 15,588 (425) | 14,295 (2274) | 3238 (631) | 5576 (1669) |
| AUC80h (ng.h/mL)d | 8262 (994) | 8393 (1044) | 3238 (631) | 5576 (1669) |
| AUC∞ (ng.h/mL)d | 16,117 (351) | 14,797 (2435) | NCf | 5512 (NCf) |
| t1/2 (h)d | 158 (17.9) | 164 (12.6) | 48.2 (12.1) | 32.1 (NCf) |
| C0/Dose (ng/mL)d | – | – | – | 718 (356) |
| Cmax/Dose (ng/mL)d | 39.5 (5.63) | 68.3 (7.03) | 31.6 (4.15) | – |
| AUClast/Dose (ng.h/mL)d | 2598 (71) | 2382 (379) | 1079 (210) | 1115 (334) |
| AUC80h/Dose (ng.h/mL)d | 1377 (166) | 1399 (174) | 1079 (210) | 1115 (334) |
| AUC∞/Dose (ng.h/mL)d | 2686 (58.5) | 2466 (406) | NCf | 1102 (NCf) |
a
n = 3 for AUClast, AUC∞ and t1/2 to include only profiles up to 672 h.
b
n = 0 for AUC∞ as values with R2adj < 0.90 and/or more than 20% extrapolation were omitted and n = 2 for t1/2 as values with R2adj < 0.90 were omitted.
c
n = 1 for AUC∞ as values with R2adj < 0.90 and/or more than 20% extrapolation were omitted and n = 1 for t1/2 as values with R2adj < 0.90 were omitted.
d
Mean (SD).
e
Median (min–max).
f
NC = not calculated as n = 0 or 1.