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Effect of Ticagrelor, a Cytochrome P450 3A4 Inhibitor, on the Pharmacokinetics of Tadalafil in Rats

College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99, Daehak-ro, Yuseong-gu, Daejeon 34134, Korea
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These authors contributed equally to this work.
Pharmaceutics 2019, 11(7), 354; https://doi.org/10.3390/pharmaceutics11070354
Received: 26 June 2019 / Revised: 15 July 2019 / Accepted: 17 July 2019 / Published: 20 July 2019
(This article belongs to the Special Issue Drug–Drug Interactions)
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Abstract

Tadalafil is a cytochrome P450 (CYP) 3A4 substrate. Because there are few data on drug-drug interactions, it is advisable to take sufficient consideration when co-administering tadalafil with CYP3A4 inducers or inhibitors. This study was conducted to assess the effect of ticagrelor, a CYP3A4 inhibitor, on the pharmacokinetic properties of tadalafil after oral administration to rats. A total of 20 Sprague–Dawley male rats were randomly divided into the non-pretreated group and ticagrelor-pretreated group, and tadalafil was orally administered to each group after pretreatment with or without ticagrelor. Blood samples were collected at predetermined time points after oral administration of tadalafil. As a result, systemic exposure of tadalafil in the ticagrelor-pretreated group was significantly increased compared to the non-pretreated group (1.61-fold), and the clearance of tadalafil in the ticagrelor-pretreated group was significantly reduced than the non-pretreated group (37%). The prediction of the drug profile through the one-compartment model could explain the differences of pharmacokinetic properties of tadalafil in the non-pretreated and ticagrelor-pretreated groups. This study suggests that ticagrelor reduces a CYP3A-mediated tadalafil metabolism and that tadalafil and a combination regimen with tadalafil and ticagrelor requires dose control and specific pharmacotherapy. View Full-Text
Keywords: tadalafil; ticagrelor; drug-drug interaction; pharmacokinetics; plasma concentration; CYP3A4 tadalafil; ticagrelor; drug-drug interaction; pharmacokinetics; plasma concentration; CYP3A4
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Na, Y.-G.; Byeon, J.-J.; Huh, H.W.; Kim, M.-K.; Shin, Y.G.; Lee, H.-K.; Cho, C.-W. Effect of Ticagrelor, a Cytochrome P450 3A4 Inhibitor, on the Pharmacokinetics of Tadalafil in Rats. Pharmaceutics 2019, 11, 354.

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