Absorption, metabolism, and excretion of [¹⁴C]YY-20394, a highly selective PI3K-Delta inhibitor in humans

Abstract

1. YY-20394, a highly selective PI3Kδ inhibitor, is under NDA submission for treating follicular lymphoma in China. The absorption, metabolism, and excretion of YY-20394 were evaluated in healthy Chinese male subjects following a single oral dose of 80 mg [¹⁴C]YY-20394 (100 µCi).

2. Within 264 h post-dose, 92.1% of the administered dose was recovered, with 58.1% from urine and 34.0% from faeces. YY-20394 was rapidly absorbed in humans, and the peak plasma concentrations occurred at 1.0 h. The absorbed drug fraction was at least 58.1% according to urine recovery.

3. In addition to the parent drug, nine metabolites were identified in plasma, urine, and faeces. Unchanged YY-20394 was the predominant drug-related component in plasma (accounting for 68.4% of the total radioactivity), urine (accounting for 90.0% of the urinary radioactivity) and faeces (accounting for 41.7% of the faecal radioactivity). In humans, the major metabolic sites were the morphine ring and side chains of piperidine rings. The major metabolic pathways involved N-dealkylation, O-dealkylation, glucuronidation and acetylation.

4. Overall, renal elimination played a significant role in the disposition of YY-20394, and the morphine ring and the side chain of the piperidine ring was the predominant metabolic sites.

Keywords:

• YY-20394
• [¹⁴C]YY-20394
• mass balance
• drug metabolism
• pharmacokinetics

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Funding

The study was sponsored by Shanghai Yingli Pharmaceutical Co., Ltd. and partially financially supported by a grant from the National Natural Science Foundation of China (No. 81903701).