TABLE 2.
Pharmacokinetic parameters of oral and intravenous BNZ in rabbitsa
| Unitb | Result for BNZ administration, mean (95% CI)c |
||||
|---|---|---|---|---|---|
| Immediate-release tablet |
i.v. (10 mg) | Extended-release tabletd |
|||
| Adult (100 mg) | Pediatric (12.5 mg) | ER-K4M (200 mg) | ER-K100M (200 mg) | ||
| kel, h−1 | 0.1955 (0.1283–0.2628) | 0.4351 (0.3366–0.5335)* | 0.2792 (0.1562–0.4023) | 0.2076 (0.1231–0.2921)† | 0.2309 (0.1464–0.3155)† |
| t1/2, h | 4.02 (2.50–5.53) | 1.66 (1.34–1.99)* | 3.07 (1.65–4.50) | 3.92 (2.45–5.41)† | 3.56 (1.96–5.17)† |
| ka, h−1 | 0.3476 (0.2971–0.3982) | 1.1472 (0.8660–1.4280)* | 0.3277 (0.2463–0.4091)† | 0.2468 (0.1736–0.3201)*,† | |
| t1/2a, h | 2.03 (1.73–2.35) | 0.63 (0.51–0.75)* | 2.24 (1.70–2.79)† | 3.19 (1.83–4.54)*,† | |
| MRT, h | 9.64 (7.88–11.42) | 3.41 (3.03–3.80)* | 3.3 (2.20–4.40)* | 12.8 (9.25–16.34)†,‡ | 19.1 (16.0–22.3)*,†,‡,§ |
| MAT, h | 2.94 (2.49–3.39) | 0.91 (0.74–1.09)* | 3.24 (2.45–5.41)† | 4.60 (2.64–6.56)*,† | |
| tmax, h | 6.0 (3.4–8.6) | 2.3 (1.6–2.9)* | 11.1 (2.9–19.4)† | 18.8 (12.9–24.8)*,† | |
| Cmax, μg/ml | 8.39 (6.11–10.67) | 0.84 (0.62–1.07)* | 10.26 (6.81–13.7)† | 7.15 (5.00–9.31)† | |
| Vz, ml/kg | 3,165 (1,394–4,936) | 1,295 (870–1,721)* | 2,338 (1,110–3,567) | 2,985 (516–5,454) | 3,190 (2,078–4,303)† |
| Cl, ml/h · kg | 515 (406–624) | 555 (336–775) | 511 (390–632) | 483 (246–720) | 668 (497–838) |
| ClR, ml/h · kg | 9.88 (5.63–14.14) | 0.46 (0–0.95)* | 1.22 (0.05–2.39)* | 8.28 (0–17.01)† | 15.68 (10.62–20.74)†,‡ |
| fe, % | 1.83 (0.96–2.71) | 0.08 (0–0.18)* | 0.21 (0–0.42)* | 1.45 (0.27–2.64)† | 2.43 (1.64–3.23)†,‡ |
Results are shown as means with 95% CIs in parentheses. n = 35 rabbits total (n=7 in each group).
kel, elimination constant; t1/2, elimination half-life; ka, absorption constant; t1/2a, absorption half-life; MRT, mean residence time; MAT, mean absorption time; Cmax, maximum plasma concentration; tmax, time to Cmax; Vz, distribution volume; Cl, total clearance; ClR, renal clearance; fe, fraction of drug excreted as unchanged in the urine.
Statistical analysis (Mann-Whitney test): *, P < 0.05 compared to the adult tablet group; †, P < 0.05 compared to the pediatric tablet group; ‡, P < 0.05 compared to the i.v. group; §, P < 0.05 compared to the ER-K4M group.
ER-K4M, extended-release tablet composed of type K4M HPMC polymer; ER-K100M, extended-release tablet composed of type K100M HPMC polymer.