The prediction of enantiomeric differences in the pharmacokinetic parameters of drugs by using a physiological perfusion model

: A physiological perfusion pharmacokinetic model was used to assess the possible differences in the model-independent pharmacokinetic parameters of drug enantiomers (total clearance, mean retention time, half-life and stationary distribution volume), depending on differences in their blood binding and in the values of intrinsic hepatic clearance. The distribution in the organs and tissues and renal clearance of enantiomers were assumed to be equal. The maximally possible values of the relationships of the above parameters were found for enantiomers. The relative values of parameters vary irregularly with the increase in the values of intrinsic hepatic clearance: drastic changes occur in the range 0 to 100 liter/hour, but they do not take place in the range 100 to 1000 liter/hour. The differences in enantiomeric parameters also decrease as the blood binding of enantiomers drops.