Kinetic parameters for the absorption of temocapril and its intracellular concentration in a rat jejunal preparation after preperfusion with BNPP
The jejunal lumen was preperfused with BNPP (400 μM) for 40 min. After washout, temocapril (100 μM) was perfused through the lumen. The rates of disappearance of temocapril (v1) and appearance of temocaprilat (v3) in the lumen, the rates of appearance of temocapril (v2) and temocaprilat (v4) in the blood vessel, the effective permeability coefficient (Peff), the apparent hydrolysis clearance (CLdeg), and the apparent absorption clearance (CLabs, temocapril) were determined. The luminal perfusate containing 100 μM temocapril was adjusted to pH 5.4 or pH 6.4 and perfused at 0.2 ml/min. The vascular perfusate (pH 7.4) flowed at 2.5 ml/min. Results are expressed as the mean ± S.D. (n = 3).
| Parameter | pH 5.4 | pH 6.4 |
|---|---|---|
| v1 (nmol/min) | 2.98 ± 0.24 | 2.44 ± 0.18 |
| v2 (nmol/min) | 0.862 ± 0.046 | 0.696 ± 0.072 |
| v3 (nmol/min) | 1.01 ± 0.11 | 1.17 ± 0.17 |
| v4 (nmol/min) | 1.01 ± 0.06 | 0.604 ± 0.139 |
| Peff (×10−3 cm/min) | 2.99 ± 0.15 | 2.32 ± 0.11 |
| CLdeg (μl/min) | 24.9 ± 3.43 | 19.5 ± 1.71 |
| CLabs, temocapril (μl/min) | 10.6 ± 1.11 | 7.64 ± 0.59 |
| CLdeg/(CLdeg + CLabs, temocapril) | 0.701 ± 0.012 | 0.718 ± 0.030 |
| Intracellular concentration (nmol/g tissue) | ||
| Temocapril | 20.6 ± 2.37 | 15.4 ± 1.08 |
| Temocaprilat | 17.0 ± 3.26 | 14.6 ± 1.23 |