Osthol, a pharmacologically active ingredient in various traditional Chinese medicines, is predominantly metabolized by CYP2C9. It may be co-administered with other drugs which are metabolized by CYP2C9 in clinical medicine. However, CYP2C9*1/*2/*3 genotype on the pharmacokinetics of osthole and its metabolic diversity between rat and human are unclear.

In this study, we investigated the effects of osthole on enzyme activity of CYP2C11/CYP2C9 in rat liver microsomes (RLMs) and human liver microsomes (HLMs), to distinguish metabolic manner of osthole in different species. Interestingly, we found that osthole inhibits the activity of CYP2C11 in a non-competitive manner in RLMs, while inhibits CYP2C9 activity in a competitive manner in pooled HLMs. Then, the effects of CYP2C9*1/*2/*3 allele on the pharmacokinetics of osthole were identified. In human CYP2C9 isoform, the Ki value of 21.93 μM (CYP2C9*1), 18.10 μM (CYP2C9*2), 13.12 μM (CYP2C9*3) indicate that there are individual differences in the inhibition of osthole on CYP2C9 activity.

We investigated how the indomethacin pharmacokinetics was affected by osthole in SD rat. To estimate the area under the curve (AUC), maximum plasma concentration (C_max) and apparent clearance (CL/F), indomethacin (10 mg/kg) was given orally combined with osthole (20 mg/kg) in adult SD rat. We found the value of PK on indomethacin, such as the AUC_0–∞, was from 176.40 ± 17.29 to 173.74 ± 27.69 μg/ml h^–1, C_max from 9.02 ± 1.24 to 9.89 ± 0.82 μg/ml and CL/F from 0.11 ± 0.01 to 0.12 ± 0.04 mg/kg/h which were unsignificantly changed compared with the control groups. However, the T_max was prolonged from 2.00 ± 0.00 h to 7.33 ± 1.15 h, and T_1/2 increased from 8.38 ± 2.30 h to 11.37 ± 2.11 h. These results indicate that osthole could potentially affect the metabolism of indomethacin in vivo.

Osthol是多种中药的药理活性成分，主要通过CYP2C9代谢。它可能与在临床医学中被CYP2C9代谢的其他药物合用。然而，尚不清楚CYP2C9 * 1 / * 2 / * 3基因型对蛇床子的药代动力学及其在大鼠和人之间的代谢多样性的影响。

在这项研究中，我们研究了蛇床子素对大鼠肝微粒体（RLM）和人肝微粒体（HLM）中CYP2C11 / CYP2C9酶活性的影响，以区分不同物种中蛇床子素的代谢方式。有趣的是，我们发现蛇床子素以非竞争性方式抑制RLM中的CYP2C9活性，而在合并的HLM中以竞争性方式抑制CYP2C9活性。然后，确定了CYP2C9 * 1 / * 2 / * 3等位基因对蛇床子素药代动力学的影响。在人CYP2C9同工型中，Ki值分别为21.93μM（CYP2C9 * 1），18.10μM（CYP2C9 * 2），13.12μM（CYP2C9 * 3），表明在抑制osthole对CYP2C9活性方面存在个体差异。

我们调查了吲哚美辛的药代动力学如何受SD大鼠中的osthole的影响。为了估计曲线下面积（AUC），最大血浆浓度（C _max）和表观清除率（CL / F），在成年SD大鼠中口服吲哚美辛（10 mg / kg）联合ostost（20 mg / kg） 。我们发现吲哚美辛的PK值（例如AUC _0–∞）为176.40±17.29至173.74±27.69μg/ ml h ^–1，C _max为9.02±1.24至9.89±0.82μg/ ml和CL / F从0.11±0.01至0.12±0.04 mg / kg / h，与对照组相比无明显变化。然而，T _max从2.00±0.00 h延长至7.33±1.15 h，并且T _1/2从8.38±2.30小时增加到11.37±2.11小时。这些结果表明，蛇床子素可能会影响吲哚美辛在体内的代谢。