A pharmacodynamic-pharmacokinetic (PD-PK) study on the effects of Danshen (Salvia miltiorrhiza) on midazolam, a model CYP3A probe substrate, in the rat

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
X WangJohn H K Yeung

Abstract

This study investigated the effect of Danshen on the pharmacodynamic-pharmacokinetic (PD-PK) effects of midazolam, a model CYP3A probe substrate. The effects of acute and 3-day Danshen treatment on the pharmacokinetics of a low dose midazolam (10 mg/kg, i.p.) were determined in vivo in the rat. Danshen (200 mg/kg, i.p.) treatment decreased midazolam clearance by 16%, with increases in the AUC by 22% and the half-life by 14%. 3-Day Danshen treatment (200 mg/kg/day, i.p.) for 3 days decreased the clearance, with increases in the T(1/2) and AUC. The effects of acute and 3-day Danshen on midazolam-induced hypnosis, serum 1'-hydroxy-midazolam to midazolam ratio and hepatic CYP3A protein expression were determined in the rat. Danshen treatments (100-200 mg/kg, i.p. and 200-500 mg/kg, p.o.) increased the sleeping time (p<0.001) produced by a hypnotic dose of midazolam (50 mg/kg, i.p.) without affecting the sleep latency. Serum 1'-hydroxy-midazolam to midazolam ratio after the hypnotic dose of midazolam was decreased after intraperitoneal Danshen treatment (200 mg/kg) but not after oral treatment at up to 500 mg/kg. All the treatment groups with Danshen, after intraperitoneal and oral administration, decreased hepatic CYP3A protein exp...Continue Reading

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May 1, 2009·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Xin WangJohn H K Yeung
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Citations

May 1, 2012·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Xuelin ZhouJohn H K Yeung
Mar 24, 2016·The Journal of Alternative and Complementary Medicine : Research on Paradigm, Practice, and Policy·Jin Gyu ChoiMyung Sook Oh
Nov 8, 2011·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Xin Wang, John Hok-Keung Yeung
Oct 3, 2012·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Xuelin ZhouJohn H K Yeung
Dec 31, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bingcong XingYan Liu
Oct 19, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Shigeru OgakiToru Maruyama
Mar 10, 2016·Drug Metabolism and Personalized Therapy·Madhav SeerviSadhana Sathaye
Mar 23, 2011·Phytotherapy Research : PTR·Xin Wang, John H K Yeung

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