3.6 Nasal administration
Approved by the FDA in May 2014, the nasal gel formulation of TTh (NATESTO®) is a product using a metered-dose pump delivering 5.5 mg of T per pump actuation, with the recommended dosing of 2 pumps (11 mg; 1 actuation/nostril) administered intranasally 3 times daily (total 33 mg/day) 6 to 8 h apart.77 Absorption occurs through the nasal mucosa, thereby avoiding hepatic first-pass metabolism, with approximately 75% of administered T entering the blood.78 Peak serum T levels were reached approximately 60 min post-application and declined to near baseline before the next dose.79, 80 In a randomized, dose-ranging, open-label phase 3 study of 306 men with TD (ClinicalTrials.gov NCT01446042), 11 mg nasal T dosed two times or three times daily resulted in between 71% and 91% of patients achieving serum TT concentrations within the defined range (10.4–36.4 nmol/L; 300–1050 ng/dl). At day 90, mean TT C avg values were 13.0 and 14.6 nmol/L (375 and 421 ng/dl) for 11 mg dosed two or three times daily, respectively.79 Compared with other routes of T delivery, nasal T gel administration results in rather low C avg and C max TT levels, as well as DHT and DHT:T ratios, even with administering 11 mg three times daily. While patients experience 3 C max peaks in 1 day because of the required 3 daily doses, only 3.3% of patients had a C max between 62.4 and 86.7 nmol/L (1800–2500 ng/dl). At day 90, the C max and C min were 32.4 nmol/L (934.9 ng/dl) and 7.0 nmol/L (200.9 ng/dl), respectively, with a peak-to-trough ratio of 4.7. Furthermore, an ongoing phase 4 clinical trial suggests that not only can T nasal gel increase serum T over time, but it can also maintain FSH, LH, and semen parameters.81
Efficacy of Nasal Testosterone Gel (Natesto®) Stratified by Baseline Endogenous Testosterone Levels
