Dual Plasma Sampling Method to Determine the Hepatic and Renal Clearance of the 2 Diastereoisomers of Gd-EOB-DTPA.

Xiaodong Yuan, Su Wang, Wenwei Shi, Yu Cai, Yingxin Chen, Ming Chen, Yanghong Peng, Guokun Ao

Investigative radiology 2020 Mar

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The aim of this study was to develop a method to determine hepatic and renal clearance of the 2 diastereoisomers (Gd-A, Gd-B) of Gd-EOB-DTPA separately. Between July 2017 and February 2018, 41 patients with hepatic disease were prospectively included. For each patient, 1 mL of iopromide (to determine glomerular filtration rate [GFR]) was coadministered with Gd-EOB-DTPA (Gd-A and Gd-B; 65:35 wt/wt). The plasma clearances of Gd-A (PCL-GdA) and Gd-B (PCL-GdB) as well as the iopromide (GFR) were generated by using dual plasma sampling method. Meanwhile, the patient's urine was collected for measurement of renal clearance of Gd-A (RCL-GdA) and Gd-B (RCL-GdB) to confirm its agreement with GFR. Hepatic clearances of Gd-A (HCL-GdA) and Gd-B (HCL-GdB) were calculated by subtracting the GFR from PCL-GdA and PCL-GdB, respectively, and were correlated with indocyanine green (ICG) 15 minutes retention rate (ICG R15). Pharmacokinetic parameters were compared between the two isomers and between Child-Pugh classifications using student's t test. Within the group of 41 patients evaluated, both RCL-GdA and RCL-GdB demonstrated a good correlation and agreement to GFR (statistics shown in the main body). HCL-GdA demonstrated a strong negative correlation (r = -0.86, P < 0.001) with ICG R15 and was much higher than HCL-GdB (116.18 ± 75.48 vs 19.74 ± 14.24 mL/min, P < 0.001). HCL-GdB demonstrated a weak correlation (r = -0.26, P = 0.102) with ICG R15. HCL-GdA of noncirrhosis and Child-Pugh class A (151.74 ± 68.28 mL/min, n = 26) was higher than that of Child-Pugh class B (54.54 ± 39.13 mL/min, n = 15; P = 0.001). A practical method was established for the determination of hepatic and renal clearance of the 2 isomers of Gd-EOB-DTPA. The 2 isomers have equal renal clearance and different hepatic clearance. The HCL-GdA may serve as a novel marker to reflect liver function reserve.

Citation

Xiaodong Yuan, Su Wang, Wenwei Shi, Yu Cai, Yingxin Chen, Ming Chen, Yanghong Peng, Guokun Ao. Dual Plasma Sampling Method to Determine the Hepatic and Renal Clearance of the 2 Diastereoisomers of Gd-EOB-DTPA. Investigative radiology. 2020 Mar;55(3):168-173