Influence of hepatic regeneration after partial hepatectomy on theophylline pharmacokinetics in rats

The influence of hepatic regeneration after partial hepatectomy on theophyl line pharmacokinetics has been studied on the rat. At different times after partial hepatectomy, theophylline was administered intravenously as a sing le dose of 6 mg/Kg. Drug plasma levels were determined by HPLC and pharmaco kinetic parameters were obtained. Physiological parameters were also measur ed. Following hepatectomy, an increase in mass liver was observed and 15 da ys after surgery, liver mass was 78% of nonhepatectomized rats. Initial the ophylline concentrations varied during the regeneration period, as well as the distribution volume at steady-estate (V-ss). Elimination half-life (t(1 /2)), notably increased after hepatectomy (7.27 +/-1.38 h), decreased with time (6.70 +/-1.18 h, 6.47 +/-0.69 and 5.17 +/-0.87 h after 24 h, 3 days an d 15 days post-hepatectomy, respectively) to reach a value close to that of the control group (4.30 +/-1.37 h). The increase in elimination half-life led to a decrease in the mean residence time during the period of liver reg eneration. However, the intrinsic clearance hardly varied during regenerati on period. We could establish the following relationship between liver weig ht (LW) and the elimination half-life: t(1/2) (h)=-0.358*LW (g)+8.6168 (R-2 =0.9906). For the mean residence time (MRT) this relationship was: MRT (h) =-0.5173*LW (g)+12.433 (R-2=0.991).