Physiologically Based Pharmacokinetic Modeling.pdf

JOURNAL OF PHARMACEUTICAL OCTOBER 1983 SCIENCES ~ VOLUME 72 NUMBER 10 ~ , .;,, ~ - - --- - - --./ 221 LITERA TURE SURVEY Physiologically Based Pharmacokinetic Modeling: Principles and Applications LEONARD E. GERLOWSKI and RAKESH K. JAIN x Received March 25,1982, from the Department of Chemical Engineering, Carnegie-Mellon University, Pittsburgh; PA 15213. ;,1226 21 Pharmacokinetic models are used to describe the body into a number of anatomical compartments, each time-dependent distribution and disposition of a substance compartment interconnected through the body fluid sys- in a living system and, as such, have numerous uses in tems. The physiologically based approach also has the clinical applications and drug design. For medicinal pur- advantages of interspecies scalability, s~cific ore-an me- poses, pharmacokinetics can be used to estimate optimal ~olimn, specific or an transport, and specific or~n drug scheduling and dosage regimens. For industrial tox- omdin res. ins, pharmacokinetics can be used to aid in determining assical pharmacokinetic techniques are used to de- safe working environments. The modeling procedure is scribe drug uptake with one- or multiple-compartmental useful in animal and clinical applications, and for obtaining systems. The solutions of differential ~quations that de- fundamental knowledge of the transport and metabolism scribe the time-dependent concentration behaviQr of the of a substance in vivo. In this paper we present a review of system consist of a series of decaying exponentials. The physiologically based pharmacokinetics in the hope of coefficients of the exponentials are fit to plasma, urinary, understanding and increasing the use of this modeling or some other obtainable tissue concentration data (4). technique. Recent review articles on the subject have Although these models are useful in many clinical situa- primarily focused on the use of physiologically based tions (5), this modeling procedure does not describe a pharmaco