TABLE 1.
Pharmacokinetic parameters of macozinone extended-release tablets F2 and F6 and immediate-release dispersible tablet after single oral administration in Beagle dogsa
| PK parameter | MCZ oral formulation and state of food intakeb |
|||||
|---|---|---|---|---|---|---|
| ER F2, fasted | ER F6, fasted | ER F2, fed | ER F6, fed | IR, fastedc | IR, fed | |
| AUC0–∞ (h·ng/mL) | ||||||
| Mean ± SD | 108.0 ± 40.0 | 550.4 ± 322.7d | 982.4 ± 60.8e | 1,021.4 ± 68.4e | 254.8 ± 105.3 | 398.0 ± 146.4 |
| Median | 105.0 | 593.0 | 963.0 | 1,055.0 | 273.5 | 435.0 |
| Range | 62.0–156.0 | 71.8–934.0 | 924.0–1,076.0 | 928.0–1,080.0 | 114.0–358.0 | 193.0–528.0 |
| AUClast (h·ng/mL) | ||||||
| Mean ± SD | 106.0 ± 40.0 | 528.1 ± 316.7d | 976.2 ± 62.8e | 1,008.4 ± 62.8e | 215.4 ± 97.9 | 322.8 ± 197.7 |
| Median | 103.0 | 522.0 | 961.0 | 1,040.0 | 223.0 | 390.0 |
| Range | 59.5–154.0 | 70.4–927.0 | 908.0–1,069.0 | 962.0–1,063.0 | 100.0–350.0 | 50.2–520.0 |
| Cmax (ng/mL) | ||||||
| Mean ± SD | 31.6 ± 5.9 | 922 ± 50.0 | 302.6 ± 74.1e | 253.2 ± 94.6 | 53.5 ± 15.2 | 146.1 ± 111.1 |
| Median | 30.0 | 181.1 | 313.0 | 204.5 | 53.4 | 142.0 |
| Range | 24.2–38.2 | 45.8–177.0 | 184.0–384.0 | 199.0–419.0 | 36.9–74.5 | 20.1–299.0 |
| Tmax (h) | ||||||
| Mean ± SD | 2.8 ± 1.3 | 5.8 ± 6.8 | 5.4 ± 0.9 | 2.7 ± 2.2 | 1.3 ± 1.1 | 0.9 ± 0.2 |
| Median | 3.0 | 3.0 | 6.0 | 1.5 | 1.0 | 1.0 |
| Range | 1.5–4.0 | 2.0–18.0 | 4.0–6.0 | 1.0–6.0 | 0.3–3.0 | 0.5–1.0 |
| kel (h−1) | ||||||
| Mean ± SD | 0.46 ± 0.07f | 0.46 ± 0.09f | 0.22 ± 0.08 | 0.16 ± 0.03 | 0.12 ± 0.04 | 0.23 ± 0.08 |
| Median | 0.42 | 0.49 | 0.18 | 0.16 | 0.11 | 0.23 |
| Range | 0.40–0.57 | 0.36–0.57 | 0.14–0.33 | 0.11–0.20 | 0.08–0.17 | 0.17–0.30 |
| t1/2 (h) | ||||||
| Mean ± SD | 1.56 ± 0.25f | 1.56 ± 0.36f | 3.48 ± 1.19 | 4.54 ± 1.02 | 6.38 ± 2.17 | 3.35 ± 1.13 |
| Median | 1.70 | 1.40 | 3.96 | 4.34 | 6.15 | 3.25 |
| Range | 1.20–1.80 | 1.20–2.00 | 2.13–4.92 | 3.50–6.05 | 4.00–9.20 | 2.30–4.60 |
| MRTlast (h) | ||||||
| Mean ± SD | 4.20 ± 1.24 | 9.08 ± 5.01d | 5.95 ± 0.69 | 5.65 ± 1.61 | 6.28 ± 1.04 | 3.64 ± 0.43 |
| Median | 3.70 | 8.30 | 6.04 | 5.95 | 6.30 | 3.50 |
| Range | 2.90–5.80 | 2.20–15.90 | 5.03–6.54 | 3.46–7.84 | 5.10–7.90 | 3.20–4.30 |
| T50%Сmax (h) | ||||||
| Mean ± SD | 2.82 ± 1.39 | 3.92 ± 2.07 | 2.87 ± 1.02 | 3.00 ± 1.64 | 2.22 ± 1.02 | 1.38 ± 0.39 |
| Median | 3.20 | 3.70 | 2.46 | 3.80 | 200 | 1.50 |
| Range | 0.90–4.60 | 1.20–7.0 | 2.20–2.74 | 1.07–4.50 | 1.20–3.60 | 0.80–1.80 |
a
Extended release tablets F2 and F6 (ER), 500 mg; immediate-release dispersible tablet (IR), 160 mg; n = 5.
b
Statistical analysis was by one-way ANOVA with Tukey’s multiple-comparison test.
c
Data are from reference 9.
d
P < 0.05, compared to the ER F2 tablet-fasted group.
e
P < 0.05, compared to the IR tablet-fed group.
f
P < 0.05, compared to the IR tablet-fasted group.