Nonlinear pharmacokinetics of indocyanine green in the rabbit and rat

The pharmacokinetic behavior of indocyanine green (ICG) in the rabbit can be described by a two-compartment open model, allowing for saturable transport of drug to the peripheral compartment and for its first-order elimination from the peripheral compartment. Use of this model led to the prediction of the accumulation of ICG in the plasma of a rabbit following the administration of repeated i.v. injections. Furthermore, studies conducted in the rat were also consistent with this model. One characteristic of the model is that above certain dose levels, the accumulation of ICG in the liver (i.e., the peripheral compartment) should reach a maximum independent of dose during certain time periods. This prediction was confirmed in a series of studies in the rat. The findings presented in this report provide evidence that a single model may be capable of explaining the variety of pharmacokinetic characteristics which have been reported for ICG, at least in the dose range studied.