Pharmacokinetics of the Liver‐Specific Contrast Agent Gd‐EOB‐DTPA in Relation to Contrast‐Enhanced Liver Imaging in Humans

Abstract

This study was performed to evaluate the effect of dose on the pharmacokinetics and efficacy of the gadolinium-based contrast medium gadoxetic acid, disodium, [gadolinium (4S)-4-(4-ethoxybenzyl)-3,6,9-tris(carboxylatomethyl)-3,6, 9-triazaundecandioic acid-disodium salt] (Gd-EOB-DTPA) as a liver-specific hepatobiliary contrast medium for computed tomography. Pharmacokinetics in serum and the pattern of elimination were investigated in 18 healthy volunteers up to 6 days after a 10-minute infusion of 0.2 mmol, 0.35 mmol, and 0.5 mmol of gadolinium per kilogram of body weight. Pharmacokinetic behavior was compared with the compute tomographic attenuation data in the liver parenchyma after the same doses in patients. Urinary and fecal excretion accounted for approximately equal portions of the administered dose. The degree of renal elimination increased with increasing doses, whereas renal clearance and half-life from urine data were not affected by dose. Dose-normalized area under the concentration-time curve was significantly increased with increasing doses indicating saturation in liver uptake for the highest dose. This finding was in agreement with the measured net increase in liver attenuation by computed tomography. Hepatic disposition revealed slight saturation phenomena for the highest dose (0.5 mmol gadolinium/kg). Nevertheless, this dose resulted in sufficient uptake by human liver, allowing for computed tomographic imaging.

Use of gadoxetate disodium for functional MRI based on its unique molecular mechanism

“…3,4 Serial dynamic MRI can demonstrate the hepatobiliary excretion and renal excretion (Figure 1). However, for those patients who have either abnormal kidney function or impaired hepatobiliary excretion, gadoxetate can still be eliminated by either the kidney or the hepatobiliary pathway unless the function of both organs are severely compromised.…”

“…7 Because the marked hepatic uptake of gadoxetate is usually reached around 20 min after contrast injection, a 20-min delayed scan is most helpful to study liver function and is known as a "hepatobiliary phase" or "hepatocyte-specific phase". 3,4 In addition, gadoxetate has a higher protein-binding capacity than Gd-DTPA does (10% vs 1.5%). This property also increases the T 1 relaxivity of gadoxetate, which implies that it can provide more intense contrast enhancement than other contrast agents.…”

“…0.025 mmol kg 21 for gadoxetate vs 0.1 mmol kg 21 for Gd-DTPA). 4 In addition, a low dose of gadoxetate may lower the incidence and severity of adverse events compared with other gadolinium contrast agents. 9,10 Membrane transport proteins for gadoxetate In hepatocytes, there are several kinds of transporters to control the influx and efflux of endogenous or exogenous molecules ( Figure 2).…”

“…20-min delayed phase), it has different pharmacokinetic and pharmacodynamic properties unlike most other extracellular gadolinium contrast agents. 3,4 Although its distribution and kinetics in the dynamic phase is similar to other gadolinium contrast agents, gadoxetate behaves differently in the hepatobiliary phase because the excretion of this agent is mediated by membrane transport proteins such as organic anion transporting polypeptides (OATPs) and multidrug resistance proteins (MRPs).…”

Contrast-enhanced magnetic resonance cholangiography with Gd-BOPTA and Gd-EOB-DTPA in healthy subjects

“…After intravenous injection, Gd-EOB-DTPA is first distributed into the extracellular space and then taken up by the hepatocytes. It is excreted unmetabolized via two pathways: 50% via the kidneys and 50% by active transport in the hepatocytes to the biliary system (18). Renal excretion can be substituted by the hepatobiliary excretion and vice versa.…”