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

Figure 3

[¹¹C]metoclopramide liver kinetics in rats () were compared 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). Liver exposure to [¹¹C]metoclopramide was described by the area under the curve (AUC) of the radioactivity kinetics in the liver (a). The rate constant of [¹¹C]metoclopramide uptake by the liver was calculated using the integration plot analysis (b). The fraction of parent [¹¹C]metoclopramide kinetics in plasma 60 min after injection is shown in (c). The plasma exposure to parent [¹¹C]metoclopramide is expressed as AUC in (d). Data regarding plasma kinetics and metabolism were calculated from Pottier et al. [14]. Data shown are mean ± SD. Statistical significance is as follows: ; ; and .

(a)

(b)

(c)

(d)