The effects of Andrographis paniculata (Burm.f.) Nees on the pharmacokinetics and pharmacodynamics of midazolam in healthy volunteers

• Main Authors: Malinee Wongnawa, Potjanee Soontaro, Wibool Riditid, Payom Wongpoowarak, Suwit Ruengkittisakul
• Format: Article
• Language: English
• Published: Prince of Songkla University 2012-11-01
• Series: Songklanakarin Journal of Science and Technology (SJST)
• Subjects: Andrographis paniculata; andrographolide; midazolam; herb-drug interaction; CYP3A4
• Online Access: http://rdo.psu.ac.th/sjstweb/journal/34-5/0475-3395-34-5-533-539.pdf

Andrographis paniculata (Burm.f.) Nees has been widely used for centuries in Asia for the treatment of common coldand diarrhea. Although it was previously reported to inhibit cytochrome P450 in vitro, the potential to cause herb-druginteraction has been questioned. The purpose of this study was to evaluate the effects of A. paniculata on the pharmacokineticsand pharmacodynamics of midazolam, a CYP3A4 probe drug, in normal healthy volunteers. The study was anopen-label, randomized, 2-phase crossover design with a 2-weeks washout period. Twelve healthy male volunteers received4 capsules of 250 mg A. paniculata 3 times a day orally for 7 days. Midazolam plasma concentration time profiles werecharacterized after a single oral dose of 7.5 mg midazolam on the day before and after A. paniculata medication. Pharmacodynamicsof midazolam were also evaluated. The results demonstrated that pretreatment with A. paniculata did not changemean pharmacokinetic parameters (Cmax, Tmax, AUC0-12, AUC0-”, T1/2, Cl/F) of oral midazolam. Since midazolam is the mostsensitive substrate for CYP3A4, thus, herb-drug interaction caused by CYP3A4 inhibition after A. paniculata in healthyvolunteers was considered not clinically relevant. However, A. paniculata potentiated the effect of midazolam in loweringblood pressure and pulse rate. Therefore, co-administration of A. paniculata with midazolam should be warranted.