The pharmacokinetic change of lidocaine by catecholamines using isolated perfused rat liver (IPRL)

We hypothesized that changes in the pharmacokinetics of lidocaine might reveal changes in portal circulation induced by catecholamines. Isolated perfused rat liver (IPRL) was selected as an experimental model, since experimental conditions in this model could be regulated. The liver was perfused with a recirculating system at a constant flow rate of 20 ml/min. Two milligrams of lidocaine was administered along with one of three drugs, dopamine, norepinephrine or adenosine triphosphate. The fractional transfer rate constants, k21 and k12, from medium to liver and liver to medium, respectively, and ke, the elimination rate constant, were calculated using a two-compartment model with the SAAM II program. Curves of decay of lidocaine from the recirculating medium consisted of a fast and a slow component. Norepinephrine and high-dose dopamine significantly increased k12, while low-dose dopamine significantly increased k21 and ke compared with control values. Thus, norepinephrine and high-dose dopamine increased lidocaine transfer rate from liver to medium, while low-dose dopamine increased the transfer rate from medium to liver and the rate of elimination from liver. These findings suggest that norepinephrine and high-dose dopamine inhibit hepatic drug uptake and that low-dose dopamine improves uptake in IPRL.