Dataset Information

Influence of OATPs on Hepatic Disposition of Erlotinib Measured With Positron Emission Tomography.

ABSTRACT: To assess the hepatic disposition of erlotinib, we performed positron emission tomography (PET) scans with [¹¹ C]erlotinib in healthy volunteers without and with oral pretreatment with a therapeutic erlotinib dose (300?mg). Erlotinib pretreatment significantly decreased the liver exposure to [¹¹ C]erlotinib with a concomitant increase in blood exposure, pointing to the involvement of a carrier-mediated hepatic uptake mechanism. Using cell lines overexpressing human organic anion-transporting polypeptides (OATPs) 1B1, 1B3, or 2B1, we show that [¹¹ C]erlotinib is selectively transported by OATP2B1. Our data suggest that at PET microdoses hepatic uptake of [¹¹ C]erlotinib is mediated by OATP2B1, whereas at therapeutic doses OATP2B1 transport is saturated and hepatic uptake occurs mainly by passive diffusion. We propose that [¹¹ C]erlotinib may be used as a hepatic OATP2B1 probe substrate and erlotinib as an OATP2B1 inhibitor in clinical drug-drug interaction studies, allowing the contribution of OATP2B1 to the hepatic uptake of drugs to be revealed.

SUBMITTER: Bauer M

PROVIDER: S-EPMC6083370 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Influence of OATPs on Hepatic Disposition of Erlotinib Measured With Positron Emission Tomography.

Bauer Martin M Matsuda Akihiro A Wulkersdorfer Beatrix B Philippe Cécile C Traxl Alexander A Özvegy-Laczka Csilla C Stanek Johann J Nics Lukas L Klebermass Eva-Maria EM Poschner Stefan S Jäger Walter W Patik Izabel I Bakos Éva É Szakács Gergely G Wadsak Wolfgang W Hacker Marcus M Zeitlinger Markus M Langer Oliver O

Clinical pharmacology and therapeutics 20171103 1

To assess the hepatic disposition of erlotinib, we performed positron emission tomography (PET) scans with [<sup>11</sup> C]erlotinib in healthy volunteers without and with oral pretreatment with a therapeutic erlotinib dose (300 mg). Erlotinib pretreatment significantly decreased the liver exposure to [<sup>11</sup> C]erlotinib with a concomitant increase in blood exposure, pointing to the involvement of a carrier-mediated hepatic uptake mechanism. Using cell lines overexpressing human organic ...[more]

PMID: 28940241

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Dataset Information

Influence of OATPs on Hepatic Disposition of Erlotinib Measured With Positron Emission Tomography.

Publications

Influence of OATPs on Hepatic Disposition of Erlotinib Measured With Positron Emission Tomography.

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