Diphenhydramine Active Uptake at the Blood-Brain Barrier and Its Interaction with Oxycodone in Vitro and in Vivo
2011 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 100, no 9, 3912-3923 p.Article in journal (Refereed) Published
Diphenhydramine (DPHM) and oxycodone are weak bases that are able to form cations. Both drugs show active uptake at the blood-brain barrier (BBB). There is thus a possibility for a pharmacokinetic interaction between them by competition for the same uptake transport system. The experiments of the present study were designed to study the transport of DPHM across the BBB and its interaction with oxycodone in vitro and in vivo. In vitro, the interaction between the drugs was studied using conditionally immortalized rat brain capillary endothelial cells (TR-BBB13 cells). The in vivo relevance of the in vitro findings was studied in rats using brain and blood microdialysis. DPHM was actively transported across the BBB in vitro (TR-BBB13 cells). Oxycodone competitively inhibited DPHM uptake with a K(i) value of 106 mu M. DPHM also competitively inhibited oxycodone uptake with a K(i) value of 34.7 mu M. In rats, DPHM showed fivefold higher unbound concentration in brain interstitial fluid (ISF) than in blood, confirming a net active uptake. There was no significant interaction between DPHM and oxycodone in vivo. This accords with the results of the in vitro experiments because the unbound plasma concentrations that could be attained in vivo, without causing adverse effects, were far below the Ki values.
Place, publisher, year, edition, pages
2011. Vol. 100, no 9, 3912-3923 p.
blood-brain barrier, drug interactions, organic cation transporters (OCTs), pharmacokinetics, active transport, HPLC (high-performance/pressure liquid chromatography), mass spectrometry
Medical and Health Sciences Pharmaceutical Sciences
Research subject Pharmacokinetics and Drug Therapy
IdentifiersURN: urn:nbn:se:uu:diva-159250DOI: 10.1002/jps.22567ISI: 000294666600030OAI: oai:DiVA.org:uu-159250DiVA: diva2:443641