[11C]glyburide PET imaging for quantitative determination of the importance of Organic Anion-Transporting Polypeptide transporter function in the human liver and whole-body
Organic Anion-Transporting Polypeptides (OATPs) are known to control the liver uptake of many drugs. Non-hepatic expression of OATPs has been reported although functional importance for whole-body pharmacokinetics (WBPK) remains unknown. Glyburide is a well described substrate of several hepatic and...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-12-01
|
| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S075333222201383X |
| _version_ | 1811221039870377984 |
|---|---|
| author | Solène Marie Louise Breuil Zacharias Chalampalakis Laurent Becquemont Céline Verstuyft Anne-Lise Lecoq Fabien Caillé Philippe Gervais Vincent Lebon Claude Comtat Michel Bottlaender Nicolas Tournier |
| author_facet | Solène Marie Louise Breuil Zacharias Chalampalakis Laurent Becquemont Céline Verstuyft Anne-Lise Lecoq Fabien Caillé Philippe Gervais Vincent Lebon Claude Comtat Michel Bottlaender Nicolas Tournier |
| author_sort | Solène Marie |
| collection | DOAJ |
| description | Organic Anion-Transporting Polypeptides (OATPs) are known to control the liver uptake of many drugs. Non-hepatic expression of OATPs has been reported although functional importance for whole-body pharmacokinetics (WBPK) remains unknown. Glyburide is a well described substrate of several hepatic and non-hepatic OATPs. Dynamic whole-body positron emission tomography (DWB-PET) with [11C]glyburide was performed in humans for determination of the importance of OATPs for liver uptake and WBPK. Seven healthy male subjects (24.7 ± 3.2 years) underwent [11C]glyburide PET scan with concomitant blood sampling. All subjects underwent baseline [11C]glyburide PET scan. Five subjects underwent a subsequent [11C]glyburide PET scan after infusion of the potent OATP inhibitor rifampicin (9 mg/kg i.v.). The transfer constant (kuptake) of [11C]glyburide from blood to the liver was estimated using the integration plot method. The tissue exposure of [11C]glyburide was described by the area under the time-activity curve (AUC) and corresponding tissue/blood ratio (AUCR). [11C]glyburide was barely metabolized in both the baseline and rifampicin conditions. Parent (unmetabolized) [11C]glyburide accounted for > 90 % of the plasma radioactivity. Excellent correlation was found between radioactive counting in arterial blood samples and in the image-derived input function, in both the baseline and rifampicin conditions (R2 = 97.9 %, p < 0.01). [11C]glyburide predominantly accumulated in the liver. Rifampicin decreased liver kuptake by 77.3 ± 7.3 %, which increased exposure in blood, kidneys, spleen, myocardium and brain (p < 0.05). No significant change in AUCR was observed except in the liver (p < 0.01). [11C]glyburide benefits from metabolic stability and high sensitivity to OATP inhibition which enables quantitative determination of OATP function. DWB-PET suggests negligible role for non-hepatic OATPs in controlling the tissue distribution of [11C]glyburide. |
| first_indexed | 2024-04-12T07:52:53Z |
| format | Article |
| id | doaj.art-020d6170d65e48a7802fb04a277edc87 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-12T07:52:53Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-020d6170d65e48a7802fb04a277edc872022-12-22T03:41:33ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-12-01156113994[11C]glyburide PET imaging for quantitative determination of the importance of Organic Anion-Transporting Polypeptide transporter function in the human liver and whole-bodySolène Marie0Louise Breuil1Zacharias Chalampalakis2Laurent Becquemont3Céline Verstuyft4Anne-Lise Lecoq5Fabien Caillé6Philippe Gervais7Vincent Lebon8Claude Comtat9Michel Bottlaender10Nicolas Tournier11Université Paris-Saclay, CEA, Inserm, CNRS, BioMaps, Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, 91401 Orsay, France; Département de Pharmacie Clinique, Faculté de Pharmacie, Université Paris-Saclay, 92296 Châtenay-Malabry, France; AP-HP, Université Paris-Saclay, Hôpital Bicêtre, Pharmacie Clinique, 94270 Le Kremlin Bicêtre, FranceUniversité Paris-Saclay, CEA, Inserm, CNRS, BioMaps, Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, 91401 Orsay, FranceUniversité Paris-Saclay, CEA, Inserm, CNRS, BioMaps, Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, 91401 Orsay, FranceAP-HP, Université Paris-Saclay, Hôpital Bicêtre, Centre de Recherche Clinique, 94270 Le Kremlin Bicêtre, France; CESP, MOODS Team, INSERM UMR 1018, Faculté de Médecine, Univ Paris-Saclay, Le Kremlin Bicêtre F-94275, FranceAP-HP, Université Paris-Saclay, Hôpital Bicêtre, Service de génétique Moléculaire, Pharmacogénétique et Hormonologie, 94270 Le Kremlin Bicêtre, France; CESP, MOODS Team, INSERM UMR 1018, Faculté de Médecine, Univ Paris-Saclay, Le Kremlin Bicêtre F-94275, FranceAP-HP, Université Paris-Saclay, Hôpital Bicêtre, Centre de Recherche Clinique, 94270 Le Kremlin Bicêtre, FranceUniversité Paris-Saclay, CEA, Inserm, CNRS, BioMaps, Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, 91401 Orsay, FranceUniversité Paris-Saclay, CEA, Inserm, CNRS, BioMaps, Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, 91401 Orsay, FranceUniversité Paris-Saclay, CEA, Inserm, CNRS, BioMaps, Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, 91401 Orsay, FranceUniversité Paris-Saclay, CEA, Inserm, CNRS, BioMaps, Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, 91401 Orsay, FranceUniversité Paris-Saclay, CEA, Inserm, CNRS, BioMaps, Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, 91401 Orsay, FranceUniversité Paris-Saclay, CEA, Inserm, CNRS, BioMaps, Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, 91401 Orsay, France; Correspondence to: CEA/SHFJ, 4 place du Général Leclerc, 91400 Orsay, France.Organic Anion-Transporting Polypeptides (OATPs) are known to control the liver uptake of many drugs. Non-hepatic expression of OATPs has been reported although functional importance for whole-body pharmacokinetics (WBPK) remains unknown. Glyburide is a well described substrate of several hepatic and non-hepatic OATPs. Dynamic whole-body positron emission tomography (DWB-PET) with [11C]glyburide was performed in humans for determination of the importance of OATPs for liver uptake and WBPK. Seven healthy male subjects (24.7 ± 3.2 years) underwent [11C]glyburide PET scan with concomitant blood sampling. All subjects underwent baseline [11C]glyburide PET scan. Five subjects underwent a subsequent [11C]glyburide PET scan after infusion of the potent OATP inhibitor rifampicin (9 mg/kg i.v.). The transfer constant (kuptake) of [11C]glyburide from blood to the liver was estimated using the integration plot method. The tissue exposure of [11C]glyburide was described by the area under the time-activity curve (AUC) and corresponding tissue/blood ratio (AUCR). [11C]glyburide was barely metabolized in both the baseline and rifampicin conditions. Parent (unmetabolized) [11C]glyburide accounted for > 90 % of the plasma radioactivity. Excellent correlation was found between radioactive counting in arterial blood samples and in the image-derived input function, in both the baseline and rifampicin conditions (R2 = 97.9 %, p < 0.01). [11C]glyburide predominantly accumulated in the liver. Rifampicin decreased liver kuptake by 77.3 ± 7.3 %, which increased exposure in blood, kidneys, spleen, myocardium and brain (p < 0.05). No significant change in AUCR was observed except in the liver (p < 0.01). [11C]glyburide benefits from metabolic stability and high sensitivity to OATP inhibition which enables quantitative determination of OATP function. DWB-PET suggests negligible role for non-hepatic OATPs in controlling the tissue distribution of [11C]glyburide.http://www.sciencedirect.com/science/article/pii/S075333222201383X[11C]glyburideHepatocyteLiverPETPharmacokineticsPositron emission tomography |
| spellingShingle | Solène Marie Louise Breuil Zacharias Chalampalakis Laurent Becquemont Céline Verstuyft Anne-Lise Lecoq Fabien Caillé Philippe Gervais Vincent Lebon Claude Comtat Michel Bottlaender Nicolas Tournier [11C]glyburide PET imaging for quantitative determination of the importance of Organic Anion-Transporting Polypeptide transporter function in the human liver and whole-body Biomedicine & Pharmacotherapy [11C]glyburide Hepatocyte Liver PET Pharmacokinetics Positron emission tomography |
| title | [11C]glyburide PET imaging for quantitative determination of the importance of Organic Anion-Transporting Polypeptide transporter function in the human liver and whole-body |
| title_full | [11C]glyburide PET imaging for quantitative determination of the importance of Organic Anion-Transporting Polypeptide transporter function in the human liver and whole-body |
| title_fullStr | [11C]glyburide PET imaging for quantitative determination of the importance of Organic Anion-Transporting Polypeptide transporter function in the human liver and whole-body |
| title_full_unstemmed | [11C]glyburide PET imaging for quantitative determination of the importance of Organic Anion-Transporting Polypeptide transporter function in the human liver and whole-body |
| title_short | [11C]glyburide PET imaging for quantitative determination of the importance of Organic Anion-Transporting Polypeptide transporter function in the human liver and whole-body |
| title_sort | 11c glyburide pet imaging for quantitative determination of the importance of organic anion transporting polypeptide transporter function in the human liver and whole body |
| topic | [11C]glyburide Hepatocyte Liver PET Pharmacokinetics Positron emission tomography |
| url | http://www.sciencedirect.com/science/article/pii/S075333222201383X |
| work_keys_str_mv | AT solenemarie 11cglyburidepetimagingforquantitativedeterminationoftheimportanceoforganicaniontransportingpolypeptidetransporterfunctioninthehumanliverandwholebody AT louisebreuil 11cglyburidepetimagingforquantitativedeterminationoftheimportanceoforganicaniontransportingpolypeptidetransporterfunctioninthehumanliverandwholebody AT zachariaschalampalakis 11cglyburidepetimagingforquantitativedeterminationoftheimportanceoforganicaniontransportingpolypeptidetransporterfunctioninthehumanliverandwholebody AT laurentbecquemont 11cglyburidepetimagingforquantitativedeterminationoftheimportanceoforganicaniontransportingpolypeptidetransporterfunctioninthehumanliverandwholebody AT celineverstuyft 11cglyburidepetimagingforquantitativedeterminationoftheimportanceoforganicaniontransportingpolypeptidetransporterfunctioninthehumanliverandwholebody AT anneliselecoq 11cglyburidepetimagingforquantitativedeterminationoftheimportanceoforganicaniontransportingpolypeptidetransporterfunctioninthehumanliverandwholebody AT fabiencaille 11cglyburidepetimagingforquantitativedeterminationoftheimportanceoforganicaniontransportingpolypeptidetransporterfunctioninthehumanliverandwholebody AT philippegervais 11cglyburidepetimagingforquantitativedeterminationoftheimportanceoforganicaniontransportingpolypeptidetransporterfunctioninthehumanliverandwholebody AT vincentlebon 11cglyburidepetimagingforquantitativedeterminationoftheimportanceoforganicaniontransportingpolypeptidetransporterfunctioninthehumanliverandwholebody AT claudecomtat 11cglyburidepetimagingforquantitativedeterminationoftheimportanceoforganicaniontransportingpolypeptidetransporterfunctioninthehumanliverandwholebody AT michelbottlaender 11cglyburidepetimagingforquantitativedeterminationoftheimportanceoforganicaniontransportingpolypeptidetransporterfunctioninthehumanliverandwholebody AT nicolastournier 11cglyburidepetimagingforquantitativedeterminationoftheimportanceoforganicaniontransportingpolypeptidetransporterfunctioninthehumanliverandwholebody |