Table 2.
Key plasma sitamaquine and desethyl-sitamaquine pharmacokinetic parameters for patients with visceral leishmaniasis, Bihar, India*
| Parameter | Day | Sitamaquine | Desethyl-sitamaquine | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Cohort 1 (n = 11) | Cohort 2 (n = 10) | Cohort 3 (n = 10) | Cohort 4 (n = 10) | Cohort 1 (n = 11) | Cohort 2 (n = 10) | Cohort 3 (n = 10) | Cohort 4 (n = 10) | ||
| AUC(0–∞), ng.hr/mL | 1 | 8,120 (73.0) | 9,143 (54.3) | 8,574 (50.3)† | 7,147 (85.3) | 572 (90.4)‡ | 500 (54.8) | 573 (55.9)† | 484 (80.2) |
| 10 | 10,416 (51.3)‡ | 14,382 (50.8) | 10,616 (49.1) | 10,696 (37.2) | 3,125 (34.4)‡ | 4,316 (57.9) | 3,694 (56.0) | 3,512 (40.4) | |
| 21 | 6,627 (21.9)§ | 8,903 (56.2) | 7,723 (59.1) | 8,350 (27.7) | 2,307 (28.7)§ | 3,163 (49.4) | 2,667 (58.7) | 3,083 (26.4) | |
| AUC(0–16), ng.hr/mL | 1 | 5,820 (84.8) | 6,161 (65.8) | 5,830 (70.0)† | 5,003 (80.1) | NC | NC | NC | NC |
| 10 | 7,468 (48.8)‡ | 9,843 (52.4) | 7,779 (48.4) | 7,814 (32.2) | NC | NC | NC | NC | |
| 21 | 4,859 (27.0)§ | 6,633 (55.3) | 5,731 (53.8) | 6,125 (27.9) | NC | NC | NC | NC | |
| Cmax, ng/mL | 1 | 626 (81.3) | 718 (56.4) | 639 (50.7) | 577 (97.8) | 36.1 (75.8) | 33.3 (49.0) | 40.8 (34.1)¶ | 30.3 (80.2) |
| 10 | 582 (50.0)‡ | 810 (43.8) | 659 (47.7) | 637 (31.5) | 148 (33.2)‡ | 214 (49.3) | 183 (56.8) | 174 (41.7) | |
| 21 | 401 (39.6)§ | 570 (53.8) | 451 (44.4) | 503 (28.4) | 109 (34.5)§ | 154 (55.2) | 127 (58.4) | 146 (21.8) | |
| t1/2, hr# | 21 | 18.9 (28.5)† | 22.8 (31.9)† | 19.3 (24.3)§ | 18.3 (24.3) | 27.1 (25.8)† | 23.0 (36.9)** | 25.5 (33.4)¶ | 27.9 (35.6)¶ |
| tmax, hr | 1 | 3.00 [1.00–24.0] | 6.00 [1.00–24.0] | 6.00 [20.0–24.0]† | 5.00 [2.00–24.0] | 23.8 (10.0–24.0) | 23.7 (16.0–24.0) | 23.8 (16.0–24.0) | 19.9 (16.0–24.0) |
| 10 | 5.96 [0–10.0]‡ | 6.00 [3.00–23.8] | 3.50 [1.75–10.0] | 4.00 [3.00–23.8] | 5.09 (0–16.0)‡ | 7.00 (3.00–23.8) | 2.42 (0.75–10.0) | 4.96 (1.00–16.0) | |
| 21 | 6.00 [3.00–10.0]§ | 4.00 [0–6.00] | 3.50 [1.97–10.0] | 4.00 [0–10.0] | 3.83 (0–16.0)§ | 2.00 (0–4.00) | 10.0 (0–16.0) | 3.50 (0–10.0) | |
*
Values are geometric mean (between-subject coefficient of variation), except for tmax, which is median [range]. AUC = area under curve; NC = not calculated; Cmax = maximum plasma concentration; t1/2 = apparent terminal half-life; tmax, = time to reach Cmax.
†
n = 8.
‡
n = 10.
§
n = 9.
¶
n = 7.
#
t1/2 was not calculated at days 1 and 10 because of the lack of adequate elimination phase concentration−time data.
**
n = 4.