PMID- 33682556 OWN - NLM STAT- MEDLINE DCOM- 20210623 LR - 20210623 IS - 1744-7658 (Electronic) IS - 1354-3784 (Linking) VI - 30 IP - 5 DP - 2021 May TI - Safety, tolerability, and pharmacokinetics of the novel pan-phosphodiesterase inhibitor ZSP1601 in healthy subjects: a double-blinded, placebo-controlled first-in-human single-dose and multiple-dose escalation and food effect study. PG - 579-589 LID - 10.1080/13543784.2021.1900822 [doi] AB - Background: The pharmacokinetics (PK), safety, and tolerability profiles of ZSP1601, a first-in-class pan-phosphodiesterase (PDE) inhibitor, were evaluated in healthy Chinese volunteers.Research design and methods: This Phase 1a study consisted of a double-blinded, randomized, placebo-controlled single ascending dose (SAD) (25 to 350 mg), multiple ascending doses (MAD) (50 or 100 mg QD), and a two-period crossover food effect study (100 mg).Results: ZSP1601 was quickly absorbed, with maximum plasma concentrations (C(max)) reached at 1.25 to 2.50 h (median T(max)). The exposures exhibited dose-proportional increases, while the mean half-life (t1/2) ranged from 6.34-8.64 h. Steady-state was reached within seven days in the MAD study. The mean steady trough concentrations were 423 and 588 ng/mL, respectively. ZSP1601 accumulation was low, with ratios