Absorption of ipratropium and L-carnitine into the pulmonary circulation of the ex-vivo rat lung is driven by passive processes rather than active uptake by OCT/OCTN transporters

Aljayyoussi, Ghaith, Price, Daniel F., Kreitmeyr, Katharina, Keogh, John P., Smith, Mathew W., Gumbleton, Mark and Morris, Christopher J ORCID: https://orcid.org/0000-0002-7703-4474 (2015) Absorption of ipratropium and L-carnitine into the pulmonary circulation of the ex-vivo rat lung is driven by passive processes rather than active uptake by OCT/OCTN transporters. International Journal of Pharmaceutics, 496 (2). pp. 834-841. ISSN 0378-5173

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Abstract

The organic cation transporters OCT and OCTN have been reported to play a significant role in the cellular uptake of substrates within in vitro lung cells. However, no studies to date have investigated the effect of these transporters upon transepithelial absorption of substrates into the pulmonary circulation. We investigated the contribution of OCT and OCTN transporters to total pulmonary absorption of L-carnitine and the anti-muscarinic drug, ipratropium, across an intact isolated perfused rat lung (IPRL). The results obtained from the IPRL were contrasted with active transport in vitro using three human pulmonary cell lines and primary rat alveolar epithelial cells. Ex-vivo studies showed that OCT/OCTN transporters do not play a role in the overall pulmonary absorption of L-carnitine or ipratropium, as evidenced by the effect of chemical inhibition of these transporters upon pulmonary absorption. In contrast, in-vitro studies showed that OCT/OCTN transporters play a significant role in cellular accumulation of substrates with preferential uptake of ipratropium by OCTs, and of L-carnitine uptake by OCTNs. The results show that in-vitro uptake studies cannot be predictive of airway to blood absorption in-vivo. Nevertheless, localised submucosal pulmonary concentrations of inhaled drugs and their pulmonary pharmacodynamic profiles may be influenced by OCT/OCTN transport activity.

Item Type:	Article
Uncontrolled Keywords:	organic cation transporters,slc22,isolated perfused rat lung (iprl),lung,pulmonary absorption,transporters, oct1,oct2,oct3,octn
Faculty \ School:	Faculty of Science > School of Pharmacy
UEA Research Groups:	Faculty of Science > Research Groups > Drug Delivery and Pharmaceutical Materials (former - to 2017) Faculty of Science > Research Groups > Pharmaceutical Materials and Soft Matter
Depositing User:	Pure Connector
Date Deposited:	19 Dec 2015 07:15
Last Modified:	31 Mar 2023 23:52
URI:	https://ueaeprints.uea.ac.uk/id/eprint/55786
DOI:	10.1016/j.ijpharm.2015.10.036

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