Background. Tanimilast is an inhaled PDE4 inhibitor currently in phase 3 clinical development for treatment of patients with COPD. The objectives of this trial were to determine the inhaled absolute bioavailability, the mass balance and route of elimination of tanimilast.

Methods. 8 healthy males received a single dose of non-radiolabeled tanimilast via NEXThaler^® 3200?g followed by a concomitant intravenous (IV) infusion of the microtracer ([¹⁴C]-tanimilast: 18.5?g and 500nCi). Collection of plasma, whole blood, urine and feces was performed up to 240h post-dose to quantify non-radiolabeled tanimilast, total [¹⁴C], [¹⁴C]-tanimilast.

Results. The inhaled absolute bioavailability of tanimilast was 49.8%. Following [¹⁴C]-tanimilast IV administration the plasma clearance was 22 L/h, the steady state volume of distribution was 201 L and the half-life was shorter compared to inhaled administration (14 vs 39 hours, respectively), suggesting slow absorption from the lung to the systemic compartment. 78.9% (70.8% in feces; 8.1% in urine) of the IV dose was recovered in excreta, as total [¹⁴C]. [¹⁴C]-tanimilast was the major radioactive component in plasma, while only 0.3% of [¹⁴C]-tanimilast was recovered in excreta (feces), indicating a predominant elimination by metabolic route. No major metabolites in plasma or excreta requiring further qualification as per FDA/EMA guidelines were detected.

Conclusion. This study design allowed for the estimation of key pharmacokinetics parameters, absolute bioavailability and route of elimination in one single trial, supporting an optimized clinical development path toward regulatory application.