]>

Table 5: Mean pharmacokinetic parameters of gliclazide before and after oral administration of pravastatin in normal rabbits ($n=5$).

Kinetic parameters Gliclazide Gliclazide + pravastatin (acute) Gliclazide + pravastatin (chronic) ${\text{AUC}}_{0\text{–}24}$ (ng/mL/h) $3905\pm 66.66$ $5034\pm {95.01}^{*}$ $5083\pm {117.10}^{*}$ ${\text{AUMC}}_{0\text{–}24}$ (ng/mL/${\text{h}}^{*}\text{h}$) $47503\pm 1653$ $57651\pm {911.50}^{*}$ $59091\pm 2941.00$ Kel (${\text{h}}^{-1}$) $0.07\pm 0.01$ $0.08\pm {0.01}^{‡}$ $0.07\pm 0.0063$ ${\text{AUC}}_{0\text{–}\infty }$ (ng/mL/h) $4963\pm 98.56$ $6182\pm {106.60}^{*}$ $6342\pm {262.20}^{‡}$ ${\text{AUMC}}_{0\text{–}\infty }$ (ng/mL/${\text{h}}^{*}\text{h}$) $88101\pm 4529$ $98882\pm {1565}^{‡}$ $105736\pm 10157$ T1/2 (h) $9.86\pm 0.39$ $8.23\pm {0.11}^{‡}$ $8.70\pm 0.63$ Ka (${\text{h}}^{-1}$) $1.15\pm 0.00$ $1.15\pm 0.00$ $1.15\pm 0.00$ Clearance (mL/h) $637.80\pm 24.05$ $513.10\pm {21.50}^{‡}$ $490.30\pm {19.07}^{‡}$ Clearance (mL/h/kg) $375.50\pm 8.34$ $301.40\pm {5.44}^{*}$ $296.00\pm 11.81$ Vdss (mL) $10704\pm 328.30$ $7765\pm {346.90}^{†}$ $7664\pm {479.10}^{‡}$ Vdss (mL/kg) $6314\pm 181.50$ $4562\pm {110.00}^{†}$ $4598\pm {144.30}^{†}$ Vdarea (mL) $9037\pm 202.50$ $6109\pm {273.80}^{†}$ $6145\pm {453.60}^{‡}$ Vdarea (mL/kg) $5335\pm 155.00$ $3589\pm {90.08}^{†}$ $3682\pm {157.70}^{†}$ MRT (h) $17.71\pm 0.64$ $15.99\pm 0.14$ $16.53\pm 0.94$ $C_{\max }$ (ng/mL) $325.80\pm 12.47$ $393.70\pm {7.37}^{†}$ $396.10\pm {17.57}^{‡}$ $T_{\max }$ (h) $3.00\pm 0.00$ $3.00\pm 0.00$ $3.00\pm 0.00$

${}^{*}$Significant at $P<.0001$; ${}^{†}$Significant at $P<.001$; ${}^{‡}$Significant at $P<.05$ compared to gliclazide control.