Table 4.
Concentrations (I; µM) and [I]/Ki of itraconazole and metformin in the liver (i.v. and p.o. studies) and intestine (p.o. study) after simultaneous single i.v. and p.o. administration of itraconazole (20 mg·kg−1) and metformin (100 mg·kg−1) to rats
| Metformin | |||||||
|---|---|---|---|---|---|---|---|
| i.v. | p.o. | ||||||
| Time (min) | Liver concentration | [I]/Ki | Time (min) | Liver concentration | [I]/Ki | Intestine concentration | [I]/Ki |
| Metformin | |||||||
| 5 | 58.7 ± 22.1 (0.159 ± 0.0496) | 6.54–9.59 | 30 | 27.1 ± 9.95 (1.21 ± 0.425) | 3.02–4.43 | 25.7 ± 9.83 (1.15 ± 0.435) | 1.67–7.51 |
| 15 | 123 ± 19.0 (1.05 ± 0.177) | 13.7–20.1 | 60 | 49.5 ± 25.7 (2.09 ± 1.22) | 5.51–8.09 | 34.0 ± 10.7 (1.35 ± 0.0336) | 2.21–9.94 |
| 30 | 65.6 ± 43.6 (1.09 ± 0.528) | 7.31–10.7 | 120 | 23.5 ± 2.04 (1.20 ± 0.314) | 2.62–3.84 | 34.0 ± 2.52 (1.78 ± 0.649) | 2.21–9.94 |
| 60 | 42.2 ± 1.23 (1.12 ± 0.135) | 4.70–6.89 | 240 | 14.9 ± 2.41 (0.996 ± 0.152) | 1.66–2.43 | 39.7 ± 3.34 (2.66 ± 0.364) | 2.58–11.6 |
| 120 | 33.7 ± 11.4 (5.64 ± 2.03) | 3.75–5.51 | 480 | 11.1 ± 3.22 (1.31 ± 0.550) | 1.24–1.81 | 26.7 ± 2.70 (3.16 ± 1.17) | 1.73–7.81 |
| 240 | 14.4 ± 6.58 (7.14 ± 6.57) | 1.60–2.35 | 720 | 5.99 ± 1.52 (1.08 ± 0.344) | 0.667–0.979 | 15.5 ± 4.72 (2.82 ± 1.08) | 1.01–4.53 |
| 480 | 3.21 ± 1.00 (2.15 ± 1.22) | 0.357–0.525 | |||||
| Itraconazole | |||||||
| 5 | 27.4 ± 2.66 (2.22 ± 0.730)* | 2.04–4.76 | 30 | 21.3 ± 7.59 (21.2 ± 7.96) | 1.59–3.70 | 27.2 ± 11.4 (27.2 ± 12.0) | 1.66–5.56 |
| 15 | 37.7 ± 4.68 (4.09 ± 1.02) | 2.81–6.55 | 60 | 38.0 ± 4.48 (9.11 ± 0.815) | 2.84–6.60 | 52.1 ± 21.8 (12.5 ± 5.17) | 3.18–10.7 |
| 30 | 37.5 ± 10.0 (6.40 ± 1.27) | 2.80–6.51 | 120 | 37.7 ± 3.60 (14.8 ± 1.42) | 2.81–6.55 | 36.2 ± 4.40 (14.3 ± 2.64) | 2.21–7.40 |
| 60 | 43.0 ± 13.2 (10.7 ± 0.802) | 3.21–7.47 | 240 | 39.6 ± 12.4 (23.4 ± 9.10) | 2.96–6.88 | 38.4 ± 9.73 (21.9 ± 3.73) | 2.34–7.85 |
| 120 | 39.9 ± 1.26 (22.4 ± 6.46) | 2.98–6.93 | 480 | 34.1 ± 3.87 (31.4 ± 3.78) | 2.54–5.92 | 33.0 ± 2.70 (30.4 ± 2.61) | 2.01–6.77 |
| 240 | 24.6 ± 9.79 (19.0 ± 10.9) | 1.84–4.27 | 720 | 22.3 ± 4.70 (25.5 ± 10.9) | 1.66–3.71 | 24.6 ± 10.2 (26.8 ± 13.7) | 1.50–5.03 |
| 480 | 22.9 ± 7.72 (40.8 ± 8.65) | 1.71–3.98 | 1800 | 15.0 ± 2.48 (41.9 ± 9.98) | 1.13–2.62 | 17.0 ± 8.93 (48.0 ± 27.2) | 1.04–3.48 |
| 720 | 17.6 ± 2.53 (55.1 ± 5.68) | 1.31–3.06 | |||||
| 1800 | 12.6 ± 2.42 (50.7 ± 24.5) | 0.940–2.188 | |||||
Data are expressed as means ± SD.
*
The values in parentheses represent the tissue-to-plasma (T/P) ratios.