Jascayd: which risks did reviewers probe?

“An increased IL-6 expression (mRNA and protein) as a consequence of usage of high doses of pan-PDE4 inhibitors has been linked to the development of mesenteric vasculitis in rat [Dietsch 2006].”

“Tissue distribution of radioactivity from whole blood into peripheral tissues appeared to be fast and extensive. In pigmented rats, there was moderate affinity of radioactivity to melanin-containing tissues of the eye, but no discernible affinity to melanin in the skin.”

“As such, there were initial concerns for vasculitis in clinical studies, an unmonitorable condition. However, in a 39-week oral repeat-dose toxicology study in monkeys, no evidence of vascular inflammation was observed at exposures exceeding those of the maximum clinical dose.”