Pharmacokinetic analysis by linear system approach I: cimetidine bioavailability and second peak phenomenon.

The pharmacokinetics of cimetidine were evaluated using a linear system analysis that was formulated specifically to resolve the second peak in the blood drug concentration profile after oral dosing. The analysis exemplifies a new approach to pharmacokinetic modeling, which appears to be a valuable alternative to linear compartmental or physiological modeling. The formulation of linear system analysis according to a certain interpretation of a pharmacokinetic phenomenon avoids the complexity of conventional modeling, which often obscures the significance of the kinetic parameters. The new approach should result in a more rational analysis of pharmacokinetic phenomena because the less important pharmacokinetic processes are not specifically modeled but are still accounted for in the mathematical treatment. The bioavailability of cimetidine calculated by deconvolution agrees with previous findings. The model proposed to describe the second peak after oral absorption appears to agree well with the data and the hepatic recycling reported for cimetidine.