Pharmacokinetic parameters describing the disposition of benazeprilat after an i.v. benazeprilat administration, a single oral, or multiple oral benazepril administrations at a nominal dose of 1168 nmol/kg in eight dogs
| Parameters (units) | Route of Administration | ||
|---|---|---|---|
| i.v. | Oral Single Dose | Oral Multiple Dose | |
| Vc (l/kg)1-a | 0.197 ± 0.022 | ||
| Vc/F (l/kg)1-b | 6.41 ± 1.43 | 4.94 ± 1.10 | |
| Cl free (l/kg/h)1-c | 0.216 ± 0.046 | ||
| Cl free/F (l/kg/h)1-d | 9.72 ± 3.97 | 5.56 ± 1.02 | |
| Bmax(nmol/kg)1-e | 23.5 ± 3.79 | ||
| Bmax(nmol/l)1-e | 119 ± 17 | 112 ± 23 | 160 ± 38 |
| Pmax(nmol/kg)1-f | 2.37 ± 0.56 | ||
| Pmax(nmol/l)1-f | 12.4 ± 4.17 | 11.7 ± 4.31 | 12.8 ± 9.4 |
| Kd(nmol/l)1-g | 4.5 ± 1.9 | 2.7 ± 1.4 | 3.9 ± 1.5 |
| fcirc (%)1-h | 10.5 ± 3.5 | 10.7 ± 3.9 | 8.4 ± 5.5 |
| t1/2 Ka(min)1-i | 19.5 [12.5–95.0] | 23.9 [2.7–83.7] | |
| t1/2 K10(min)1-j | 39 ± 6 | 31 ± 12 | 36 ± 9 |
| F%1-k | 2.57 ± 1.23 | 3.95 ± 0.83 | |
| t lag (min)1-l | 11.0 ± 10.8 | 1.58 [0.77–7.99] | |
Values are mean ± S.D. or median [range].
↵1-a Vc, volume of distribution of the free fraction; free fraction must be understood as actually free plus fraction not specifically bound to plasma protein.
↵1-b Vc/F, apparent volume of distribution with respect to the bioavailability.
↵1-c Clfree, clearance of the free fraction calculated by K10 × Vc with K10, the rate constant of elimination of the free fraction and Vc as defined above.
↵1-d Clfree/F, apparent clearance of the free fraction with respect to the bioavailability.
↵1-e Bmax, total binding capacity (circulating and noncirculating converting enzyme) expressed in amount term (nanomoles per kilogram) or scaled by Vc (nanomoles per liter)
↵1-f Pmax, plasma binding capacity (circulating converting enzyme) calculated by Bmax× fcirc expressed in amount term (nanomoles per kilogram) or scaled by Vc (nanomoles per liter)
↵1-g Kd, concentration of free benazeprilat producing saturation of 50% of converting enzyme (circulating and noncirculating).
↵1-h fcirc, fraction of total binding site (Bmax) that is not bound to tissue, i.e., free in the volume of distribution.
↵1-i t1/2 Ka, half-life of benazeprilat invasion.
↵1-j t1/2 K10, half-life of elimination of the free fraction.
↵1-k F%, absolute bioavailability of benazeprilat from benazepril.
↵1-l t lag, lag time to absorption of benazepril and/or conversion of benazepril into benazeprilat.