FIG. 4.
Three-compartment pharmacokinetic model for comodelling intravenous and oral administration of dOTC. The model describes the disposition of both (−) and (+) dOTC when dOTC is administered. Intravenous doses are infused into the central compartment; oral doses are bolused into the absorptive site. Abbreviations: A, site of absorption into which oral doses are administered; ka, rate constants of oral absorption; Tlag, associated lag times describing oral absorption; D%, percentage of the total administered dose absorbed in each phase of oral absorption; Vc, volume of the central compartment; Vpf, volume of the fast equilibrating peripheral compartment; Vps, volume of the slow equilibrating peripheral compartment; CLdf, distributional clearance between the central and fast equilibrating peripheral compartments; CLds, distributional clearance between the central and slow equilibrating peripheral compartments; CLt, drug clearance out of the central compartment. (−) and (+) symbols refer to the (−) and (+) stereoisomers of dOTC, respectively.