School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
J Pharm Pharmacol. 2010 Aug;62(8):1077-83. doi: 10.1111/j.2042-7158.2010.01127.x.
The effects of the aqueous extract of Salvia miltiorrhiza Bunge (Danshen) on metabolism/pharmacokinetics of caffeine and on liver microsomal CYP1A2 activity in humans and rats have been investigated.
The effects of Danshen aqueous extract on CYP1A2 activity were determined by metabolism of model substrates in the rat in vivo and in humans and rats in vitro. HPLC was used to determine model substrates and metabolites.
In the rat, single dose Danshen aqueous extract treatment (100 or 200 mg/kg, i.p.) decreased metabolism of caffeine to paraxanthine, with overall decrease in caffeine clearance (6-20%), increase in area under the curve (AUC; 7-24%) and plasma half-life (t(1/2) 14-16%). Fourteen-day Danshen aqueous extract treatment (100 mg/kg/day, i.p. or 200 mg/kg/day, p.o.) decreased caffeine clearance (16-26%), increased AUC (18-31%) and prolonged plasma t(1/2) (8-10%). Aqueous extract of Danshen (125-2000 microg/ml) competitively inhibited human and rat liver microsomal CYP1A2 activity with inhibition constant (K(i)) values at 190 and 360 microg/ml, respectively.
These studies demonstrated that Danshen aqueous extract affected the metabolism of CYP1A2 substrates through competitive inhibition and altered their clearance.
研究丹参水提物对咖啡因代谢/药代动力学的影响及其对人及大鼠肝微粒体 CYP1A2 活性的影响。
采用大鼠体内和人及大鼠体外模型底物代谢法，测定丹参水提物对 CYP1A2 活性的影响。采用 HPLC 测定模型底物及代谢物。
在大鼠中，单次给予丹参水提物（100 或 200mg/kg，ip）处理可降低咖啡因转化为对-黄嘌呤的代谢，导致咖啡因清除率总体下降（6-20%），曲线下面积（AUC；7-24%）和血浆半衰期（t(1/2) 14-16%）增加。连续 14 天给予丹参水提物（100mg/kg/天，ip 或 200mg/kg/天，po）处理可降低咖啡因清除率（16-26%），增加 AUC（18-31%），延长血浆 t(1/2)（8-10%）。丹参水提物（125-2000μg/ml）对人及大鼠肝微粒体 CYP1A2 活性呈竞争性抑制，抑制常数（K(i)）值分别为 190 和 360μg/ml。
这些研究表明，丹参水提物通过竞争性抑制作用影响 CYP1A2 底物的代谢，并改变其清除率。
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