Enhanced Bioavailability of Tadalafil after Intranasal Administration in Beagle Dogs

• Main Authors: Jeong-Soo Kim, Min-Soo Kim, In-hwan Baek
• Format: Article
• Language: English
• Published: MDPI AG 2018-10-01
• Series: Pharmaceutics
• Subjects: tadalafil; pharmacokinetics; intranasal; modeling; dog
• Online Access: http://www.mdpi.com/1999-4923/10/4/187

Tadalafil is an oral selective phosphodiesterase type-5 inhibitor with demonstrated efficacy and safety that is used to treat erectile dysfunction. The purpose of this study is to compare the pharmacokinetic properties of tadalafil after conventional oral tablet administration and novel intranasal administration in beagle dogs. Fourteen 13-month-old male beagle dogs were randomly divided into two groups, and were given 5 mg tadalafil orally or intranasally in a parallel design. Blood samples were collected before and 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 36 h after administration. The plasma concentration of tadalafil was determined via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The systemic exposure and absorption rate of tadalafil were significantly greater in the intranasal administration group than in the oral administration group. A one-compartment model with first-order absorption and elimination was sufficient to explain the pharmacokinetic characteristics observed after both oral and intranasal administration. This study indicates that the development of tadalafil nasal delivery systems is feasible and may lead to better results than the conventional oral route.