Distribution of lenalidomide into semen of healthy men after multiple oral doses.

Lenalidomide is a thalidomide analog and an immunomodulatory drug with demonstrated efficacy in various hematological malignancies. The distribution of lenalidomide into semen was evaluated in healthy subjects. Twenty-four male subjects were randomized into 4 equal groups for semen collection. All subjects received lenalidomide 25 mg once daily for 4 days. After the last dose, a single semen sample was collected from subjects, at approximately 2, 24, 72, and 168 hours for groups 1, 2, 3, and 4, respectively, and serial blood sampling was performed for 24 hours in all groups. The mean lenalidomide concentration in semen was 478 ng/mL at 2 hours and 10.0 ng/mL at 24 hours, which was higher than was the corresponding drug concentration in plasma (219 ng/mL at 2 hours and undetectable at 24 hours) but roughly paralleled the time course in plasma for drug elimination. The mean amount of lenalidomide was 1379 ng/ejaculate at 2 hours and 35 ng/ejaculate at 24 hours. The maximal drug content in a single ejaculate was <2000 ng (<0.01% of the daily 25-mg dose). Lenalidomide was undetectable in semen at 72 and 168 hours. Therefore, lenalidomide is essentially eliminated from seminal reservoirs by 72 hours postdose.