Malinee Wongnawa, Potjanee Soontaro, Wibool Riditid, Payom Wongpoowarak and Suwit Ruengkittisakul

pp. 533 - 539

Abstract

Andrographis paniculata (Burm.f.) Nees has been widely used for centuries in Asia for the treatment of common cold
and diarrhea. Although it was previously reported to inhibit cytochrome P450 in vitro, the potential to cause herb-drug
interaction has been questioned. The purpose of this study was to evaluate the effects of A. paniculata on the pharmacokinetics and pharmacodynamics of midazolam, a CYP3A4 probe drug, in normal healthy volunteers. The study was an
open-label, randomized, 2-phase crossover design with a 2-weeks washout period. Twelve healthy male volunteers received
4 capsules of 250 mg A. paniculata 3 times a day orally for 7 days. Midazolam plasma concentration time profiles were
characterized after a single oral dose of 7.5 mg midazolam on the day before and after A. paniculata medication. Pharmacodynamics of midazolam were also evaluated. The results demonstrated that pretreatment with A. paniculata did not change
mean pharmacokinetic parameters (C_max
, T_max
, AUC_0-12, AUC_0-”, T_1/2, Cl/F) of oral midazolam. Since midazolam is the most
sensitive substrate for CYP3A4, thus, herb-drug interaction caused by CYP3A4 inhibition after A. paniculata in healthy
volunteers was considered not clinically relevant. However, A. paniculata potentiated the effect of midazolam in lowering
blood pressure and pulse rate. Therefore, co-administration of A. paniculata with midazolam should be warranted.

Keywords

• Andrographis paniculata
• andrographolide
• midazolam
• herb-drug interaction
• CYP3A4