Drug disposition as determined by the interplay between drug-transporting and drug-metabolizing systems

Modeling of Intestinal Drug Absorption: Roles of Transporters and Metabolic Enzymes (For the Gillette Review Series)

“…Adapted from Tam et al (2003), with permission. clusion also agrees with intuitive and deductive reasoning since reduction of intracellular substrate concentration in the intestine accompanies drug efflux at the apical membrane, yielding lower rates of intestinal metabolism (Sirianni and Pang, 1997;Schuetz and Schinkel, 1999). This was also found in a simulation study based on Caco-2 cell efflux and metabolism (Tam et al, 2003a).…”

The Roles of Transporters and Enzymes in Hepatic Drug Processing

“…Hence, secretion removes the cellular substrate from enzymes and reduces the rates of metabolism, although the extent of metabolism ultimately will not be altered (Tam et al, 2003). This view complies with those of others who state that a competing pathway detracts from other pathways due to reduction of the substrate concentration (Morris and Pang, 1987;Sirianni and Pang, 1997;Ito et al, 1999;Schuetz and Schinkel, 1999).…”

Glucuronidation and the Transport of the Glucuronide Metabolites in LLC-PK1 Cells

“…Recently, it has been hypothesized that the activities of transporters and metabolizing enzymes are coupled. 2,21, [33][34][35][36][37][38] These new findings suggest that LLC-PK1 may provide a useful model to study the possible relationship between glucuronidation and drug transporters.…”

“…Although information regarding the porcine UGT genetics is still unknown, it may be worthwhile in the future to examine what porcine UGT isoforms are expressed in LLC-PK1 and how they compare to human UGTs. Recently, it has been hypothesized that the activities of transporters and metabolizing enzymes are coupled. ,,− These new findings suggest that LLC-PK1 may provide a useful model to study the possible relationship between glucuronidation and drug transporters.…”