Prediction of the Possibility of the Second Peak of Drug Plasma Concentration Time Curve after iv Bolus Administration from the Standpoint of the Traditional Multi-Compartmental Linear Pharmacokinetics

It is shown that the existence of the second peak on the drug plasma concentration time curve Cp(t) after iv bolus dosing can be explained by considering the traditional multi-compartmental linear pharmacokinetics. It was found that a direct solution of the general three-compartment model yields the second peak of Cp(t) for the certain values of the rate constants, and Cp(t) includes the term with oscillating preexponent, that is, K sin(ωt + ϕ) exp(−λt), in this case. The considered model describes the drug entero-hepatic recirculation in the species which do not have gall bladder (rats). The model fit of the experimental data from rat pharmacokinetic studies where the second peak of Cp(t) was observed, yields the rate of bile production that is consistent with the physiological value (∼0.7 mL/h).