Mass balance study of [¹⁴C]SHR0302, a selective and potent JAK1 inhibitor in humans

Effect of CYP3A4 induction and inhibition on the pharmacokinetics of SHR0302 in healthy subjects

“…In vitro studies revealed SHR0302 was a substrate of P‐glycoprotein (P‐gp) and breast cancer resistance protein (BCRP), which may play a role in excreting the parent drug into faeces. The predominant metabolite SHR161279 (product of monooxidation) of SHR0302 was present at 33.6% in urine and 6% in faeces 9 . The in vitro studies identified cytochrome P450 (CYP) 3A4 and CYP2C8 as the primary enzymes involved in SHR0302 metabolism, with CYP2D6 playing a lesser role (unpublished data).…”

“…SHR0302 was rapidly absorbed after oral administration, with a median time to reach maximum concentration of 1.0 h and a mean half‐life of 8.95–9.36 h (Hengrui study SHR0302‐101 unpublished data). In a human mass balance study, 9 unchanged SHR0302 accounted for approximately 90% of the total radioactivity in plasma, while no major metabolite (>10%) was detected. Approximately 5% and 24% of the dose were eliminated as the unchanged parent drug in urine and faeces.…”

“…The predominant metabolite SHR161279 (product of monooxidation) of SHR0302 was present at 33.6% in urine and 6% in faeces. 9 The in vitro studies identified cytochrome P450 (CYP) 3A4 and CYP2C8 as the primary enzymes involved in SHR0302 metabolism, with CYP2D6 playing a lesser role (unpublished data). Of these enzymes, CYP3A4 was identified as the key enzyme for N-demethylation and monooxidation.…”