Positron Emission Tomography Imaging Reveals an Importance of Saturable Liver Uptake Transport for the Pharmacokinetics of Metoclopramide

Figure 2

PET kinetics in the rat liver () were measured in the absence (µ dose) and the presence of a pharmacologic dose of metoclopramide (3 mg/kg, Meto), with or without P-gp inhibition using i.v. tariquidar (8 mg/kg) (TQD). Time-activity curves of radioactivity obtained in the liver after injection of [¹¹C]metoclopramide are shown in (a). The fitted curves (dashed lines) corresponding to the mean plasma kinetics of parent [¹¹C]metoclopramide are shown in (b). Plasma kinetics were obtained from previously reported experiments performed in the same conditions ( animals per condition) [14]. The mean integration plots (dashed line) used to calculate the transfer constant of [¹¹C]metoclopramide from plasma to the liver are shown in (c). See Materials and Methods for definition of variables used in integration plot analysis. The liver uptake rate constants correspond to the slope of the linear regression lines, calculated from 2 to 7.5 min after injection. Data shown are mean ± SD.

(a)

(b)

(c)