Table 4.
Summary of Pharmacokinetic Parameters for Multiple Ascending Dose (MAD) of Benfotiamine
| Analytes | Parameters | MAD | |||||
|---|---|---|---|---|---|---|---|
| 150 mg (n=12) | 300 mg (n=12) | 600 mg (n=12) | |||||
| Day 1 | Day 10 | Day 1 | Day 10 | Day 1 | Day 10 | ||
| TM | AUC0-t, ng·h/mL | 1639.8 (322.8) | 3795.1 (700.4) | 4902.9 (780.8) | 11,081.3 (1237.2) | 13,493.8 (2185.3) | 31,855.0 (4967.3) |
| Cmax, ng/mL | 276 (57) | 439 (84) | 624 (104) | 1089 (131) | 1485 (208) | 2783 (470) | |
| Tmax, h | 1.5 (0.5–2.5) | 1.5 (0.5–2.0) | 1.5 (1.0–3.5) | 1.8 (0.5–4.0) | 2.0 (1.0–3.0) | 2.0 (1.5–3.0) | |
| t1/2, h | 37.2 (21.0) | 36.48 (8.1) | 29.0 (8.9) | 25.97 (4.62) | 16.8 (3.6) | 16.46 (3.07) | |
| CL/F, L/h | 90.1 (18.8) | 37.57 (6.92) | 61.2 (9.5) | 26.54 (3.02) | 45.2 (7.2) | 18.97 (2.95) | |
| Vd/F, L | 4522 (2119) | 1969 (537) | 2609 (1052) | 1008 (275) | 1112 (356) | 455 (127) | |
| AUC0-τ, ng·h/mL | 1334.4 (245.3) | 2614.0 (476.6) | 3694.8 (551.8) | 7481.91 (763.0) | 9428.3 (1392.1) | 19,824.0 (2968.6) | |
| Cmin, ng/mL | – | 107 (28) | – | 363 (51) | – | 1104 (195) | |
| Cav, ng/mL | – | 218 (40) | – | 623 (64) | – | 1652 (247) | |
| Rac | – | 1.96 (0.16) | – | 2.05 (0.22) | – | 2.11 (0.16) | |
| Rac, Cmax | – | 1.60 (0.15) | – | 1.78 (0.28) | – | 1.88 (0.24) | |
| TDP | AUC0-t, ng·h/mL | 2198.9 (640.5) | 4009.8 (1089.1) | 2984.0 (681.9) | 5141.4 (1342.2) | 3588.6 (1356.3) | 5617.7 (1958.9) |
| Cmax, ng/mL | 68 (19) | 111 (31) | 79 (20) | 126 (35) | 77 (30) | 126 (40) | |
| Tmax, h | 8.0 (6.0–12.0) | 1.5 (0.0–6.0) | 12.0 (8.0–12.0) | 1.8 (0.0–12.0) | 12.0 (6.0–36.0) | 2.0 (0.0–12.0) | |
| t1/2, h | 67.4 (61.1) | 51.2 (26.4) | 34.3 (17.9) | 37.4 (10.5) | 28.7 (5.0) | 41.7 (16.1) | |
| CL/F, L/h | 44.0 (15.9) | 27.7 (9.2) | 83.9 (27.6) | 46.6 (15.2) | 150.0 (54.0) | 80.9 (21.6) | |
| Vd/F, L | 3396 (1304) | 1950 (1099) | 3809 (1261) | 2446 (804) | 6129 (2265) | 4777 (2117) | |
| AUC0-τ, ng·h/mL | 620.8 (206.9) | 1147.0 (333.3) | 654.4 (134.5) | 1338.3 (404.5) | 640.2 (232.8) | 1230.8 (390.1) | |
| Cmin, ng/mL | – | 101 (32) | – | 113 (34) | – | 106 (38) | |
| Cav, ng/mL | – | 96 (28) | – | 112 (34) | – | 103 (33) | |
| Rac | – | 1.88 (0.19) | – | 2.03 (0.32) | – | 1.97 (0.25) | |
| Rac, Cmax | – | 1.62 (0.15) | – | 1.59 (0.20) | – | 1.69 (0.24) | |