Formulation and Particle Size Reduction Improve Bioavailability of Poorly Water-Soluble Compounds with Antimalarial Activity
Table 3
Evaluations* of pharmacokinetics and drug distribution in liver of decoquinate (DQ) at dose of 80 mg/kg with various formulations in male ICR mice (n = 5) following single intragastric administration.
PK parameters
Decoquinate in plasma
Decoquinate in liver
Microsuspension (36.88 μm)
Nanosuspension (0.39 μm)
Microsuspension (36.88 μm)
Nanosuspension (0.39 μm)
(ng/mL or g)
6.1 ± 0.7
25.3 ± 2.9
93.4 ± 9.7
407.3 ± 54.4
(hr)
6.50 ± 2.12
3.66 ± 1.16
6.50 ± 2.12
3.00 ± 2.00
AUClast (ng·h/mL or g)
46.2 ± 2.5
367.9 ± 26.8
1057.4 ± 184.8
5768.7 ± 1104.8
AUCinf. (ng·h/mL or g)
51.4 ± 6.2
795.5 ± 36.19
1096.2 ± 170.3
6055.5 ± 1116.1
elimination (β, h)
8.17 ± 2.59
23.93 ± 14.20
5.12 ± 0.40
6.36 ± 1.43
Vz/F (liter/kg)
3652.3 ± 732.4
925.7 ± 505.3
—
—
CL/F (liter/hr/kg)
313.6 ± 37.6
117.8 ± 58.9
—
—
MRT (h)
7.47 ± 0.79
4.51 ± 0.71
7.16 ± 0.42
7.51 ± 0.58
Relative bioavailability (%)
6.77
100
—
—
Drug distribution in liver
—
—
18.1
100
The data was fitted with Phoenix/WinNonlin (V6.1). PK: pharmacokinetics; MRT: mean residence time.
