Preclinical pharmacokinetics of 4-hydroxy isoleucine using LC–MS/MS: a potential polycystic ovary syndrome phytopharmaceutical therapeutics: supplementary tables

Aim: To study the preclinical pharmacokinetics of 4-hydroxy isoleucine (4-HIL) targeted for polycystic
ovary syndrome. Methodology: The quantitative bioanalysis of 4-HIL in different biological matrices
in female Sprage-Dawley rats using LC–MS/MS. Results: At 50 mg/kg, 4-HIL had 56.8% absolute
oral bioavailability. It was quickly absorbed and distributed in various tissues in order of small
intestine > kidney > ovary > spleen > lung > liver > heart > brain after oral administration. Moreover,
11.07% of 4-HIL was recovered in urine and feces within 72 h. Conclusion: 4-HIL levels in vital organs were
found safe, as per tissue distribution results. Hence, 4-HIL could be used as promising therapeutics for
management of polycystic ovary syndrome.

研究目的：探究针对多囊卵巢综合征（polycystic ovary syndrome）的4-羟基异亮氨酸（4-hydroxy isoleucine，4-HIL）的临床前药代动力学特性。
研究方法：采用液相色谱-串联质谱法（LC–MS/MS），对雌性斯普拉格-道利大鼠的多种生物基质中的4-HIL进行定量生物分析。
研究结果：以50 mg/kg剂量给药时，4-HIL的绝对口服生物利用度为56.8%。口服给药后，4-HIL可被快速吸收并分布至各组织，组织分布优先级依次为小肠＞肾脏＞卵巢＞脾脏＞肺脏＞肝脏＞心脏＞大脑。此外，72小时内可在尿液与粪便中回收到11.07%的4-HIL。
研究结论：基于组织分布结果，关键脏器中的4-HIL水平均处于安全范围。因此，4-HIL有望成为治疗多囊卵巢综合征的潜在候选治疗药物。