Table 2.
Pharmacokinetic parameters of DA-8159 and DA-8164 after single p.o. administration of DA-8159 at a dose of 30 mg kg−1 without and with simultaneous single p.o. administration of terazosin at a dose of 5 mg kg−1, and of terazosin after single p.o. administration of terazosin at a dose of 5 mg kg−1 without and with simultaneous single p.o. administration of DA-8159 at a dose of 30 mg kg−1 to rats
| Parameter |
DA-8159 |
Parameter |
Terazosin |
||
|---|---|---|---|---|---|
| Without terazosin | With terazosin | Without DA-8159 | With DA-8159 | ||
| DA-8159 | Terazosin | ||||
| AUC (μg min ml−1) | 133±62.4 | 137±30.3 | AUC (μg min ml−1) | 134±33.5 | 235±49.7a |
| Terminal t1/2 (min) | 298±50.8 | 306±139 | Terminal t1/2 (min) | 303±119 | 208±53.6 |
| CLR (ml min−1 kg−1) | 1.91±1.21 | 1.89±1.18 | CLR (ml min−1 kg−1) | 4.64±0.824 | 5.97±1.77b |
| Cmax (μg ml−1) | 0.305±0.0883 | 0.274±0.0775 | Cmax (μg ml−1) | 0.303±0.242 | 0.631±0.118c |
| Tmax (min) | 30 (15–90) | 30 (15–45) | Tmax (min) | 30 (15–360) | 45 (30–60) |
| Ae0–24 h (% of DA-8159 dose) | 0.878±0.259 | 1.09±0.480 | Ae0–24 h (% of terazosin dose) | 12.4±2.28 | 29.5±7.31a |
| GI24 h (% of DA-8159 dose) | 2.10±3.20 | 1.52±0.956 | GI24 h (% of terazosin dose) | 7.04±3.38 | 1.48±1.06a |
| F (%) | 25.9 | 24.8 | F (%) | 67.8 | 73.9 |
| DA-8164 | |||||
| AUC (μg min ml−1) | 104±35.4 | 114±34.0 | |||
| Terminal t1/2 (min) | 153±47.0 | 194±71.0 | |||
| CLR (ml min−1 kg−1) | 0.428±0.224 | 0.227±0.345 | |||
| Cmax (μg ml−1) | 0.272±0.106 | 0.201±0.0583 | |||
| Tmax (min) | 180 (60–360) | 45 (30–480) | |||
| Ae0–24 h (% of DA-8159 dose) | 0.176±0.113 | 0.108±0.0492 | |||
| GI24 h (% of DA-8159 dose) | 0.654±0.286 | 0.621±0.258 | |||
Abbreviations: AUC, total area under the plasma concentration–time curve from time zero to time infinity; CLR, time-averaged renal clearance; Cmax, peak plasma concentration; t1/2, half-life; Tmax, time to reach a Cmax; Ae0–24 h, percentage of dose excreted in 24 h urine; F, extent of absolute oral bioavailability; GI24 h, percentage of dose recovered from the entire gastrointestinal tract (including its contents and feces) at 24 h; p.o., per os.
Data are expressed as mean±s.d., (without terazosin, n=8; with terazosin, n=8 for DA-8159, without DA-8159, n=7; with DA-8159, n=8 for terazosin). Significant difference from without DA-8159,
P<0.001,
P<0.05 and
P<0.01.