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Article

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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Authors to whom correspondence should be addressed.
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)
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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MDPI and ACS Style

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. https://doi.org/10.3390/pharmaceutics11070354

AMA Style

Na Y-G, Byeon J-J, Huh HW, Kim M-K, Shin YG, Lee H-K, Cho C-W. Effect of Ticagrelor, a Cytochrome P450 3A4 Inhibitor, on the Pharmacokinetics of Tadalafil in Rats. Pharmaceutics. 2019; 11(7):354. https://doi.org/10.3390/pharmaceutics11070354

Chicago/Turabian Style

Na, Young-Guk, Jin-Ju Byeon, Hyun W. Huh, Min-Ki Kim, Young G. Shin, Hong-Ki Lee, and Cheong-Weon Cho. 2019. "Effect of Ticagrelor, a Cytochrome P450 3A4 Inhibitor, on the Pharmacokinetics of Tadalafil in Rats" Pharmaceutics 11, no. 7: 354. https://doi.org/10.3390/pharmaceutics11070354

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