ArticleEuropean journal of drug metabolism and pharmacokinetics2017
Liver Perfusion Modifies Gd-DTPA and Gd-BOPTA Hepatocyte Concentrations Through Transfer Clearances Across Sinusoidal Membranes.
Article in European journal of drug metabolism and pharmacokinetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 11 citations in OpenAlex.
- Liver enhancement during hepatobiliary phase after Gd-BOPTA administration: correlation with liver and renal function.European radiology · 2021Article
- Application of ultrasound combined with enhanced MRI by Gd-BOPTA in diagnosing hepatocellular carcinoma.American journal of translational research · 2021Article
- Isolated Perfused Rat Livers to Quantify the Pharmacokinetics and Concentrations of Gd-BOPTA.Contrast media & molecular imaging · 2018Article
- Comparison of the Ability of Gadobenate Dimeglumine and Gadolinium Ethoxybenzyl Dimeglumine to Display the major Features for Noninvasively Diagnosing Hepatocellular Carcinoma According to the LI-RADS 2018v.Technology in cancer research & treatmentArticle
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesGadobenate dimeglumine (Gd-BOPTA) is a commercialised hepatobiliary contrast agent used during liver magnetic resonance imaging (MRI) to detect liver diseases. It enters into human hepatocytes through organic anion transporting polypeptides (OATP1B1/B3) and crosses the canalicular transporter multiple resistance-associated protein 2 (MRP2) to be excreted into bile canaliculi. Gd-BOPTA can return to sinusoids via the sinusoidal transporters MRP3/MRP4. Hepatocyte concentrations of Gd-BOPTA depend on three clearances: the sinusoidal clearance or volume of sinusoidal blood cleared of drugs per unit of time and two hepatocyte clearances (into bile canaliculi or back to sinusoids) or volume of hepatocytes cleared of drugs per unit of time in the respective liver compartments. The present study investigates whether changing liver blood flow modifies hepatocyte concentrations when plasma concentrations do not change.
methodsWe perfused normal rat livers at various portal flow rates (24, 30, and 36 ml/min) with 200 µM Gd-BOPTA and measured sinusoidal clearances, hepatocyte clearances, and hepatocyte concentrations of Gd-BOPTA.
resultsWe showed that varying portal flow rates changes the sinusoidal clearance of Gd-BOPTA despite its low extraction ratio. Portal flow rates do not modify Gd-BOPTA clearance from hepatocytes into bile canaliculi but can change hepatocyte clearance back to sinusoids.
conclusionAt a given perfused concentration, portal flow rates modify Gd-BOPTA hepatocyte concentrations, a result important to consider when interpreting liver imaging.
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