Clinical Evidence

Effect of a herbal extract containing Curcumin and Piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers
Br J Clin Pharmacol. 2013; 75(2):450-62
Today Curcuminoids have been evaluated for management for several health conditions including Alzheimer’s dementia, cancer and other inflammatory conditions. However, higher doses are required to compensate its low bioavailability. It has been seen in previous studies that Piperine, a major constituent of black pepper extract can enhance oral bioavailability of Curcumin by 20 fold.


To evaluate whether the commercially available Curcuminoids-Piperine extract alters pharmacokinetics disposition of probe drugs for metabolized by enzymes such as CYP3A, CYP2C9, UGT and SULT.

Study Design:

A randomized, placebo controlled six period cross over study was planned with eight subjects. A standardized Curcuminoids-Piperine combination containing 500 mg of Curcuminoids and 3 mg of Piperine was administered at dosage to provide 4 g of Curcuminoids and 24 mg of Piperine. The probe drugs included Midazolam (3 mg), Flurbiprofen (100 mg), paracetamol (325 mg) and were orally given either with Curcuminoids-Piperine combination or placebo resulting in six different treatment conditions. The study was blinded towards Curcuminoids-Piperine combination and placebo treatment but not to probe drugs.

To understand the effect of Curcuminoids-Piperine combination on the probe drugs and ascertain the baseline values, the Curcuminoids-Piperine combination was given orally with water in morning and evening before the day of administration of probe drugs and next day baseline plasma sample was collected. The third dosage of Curcuminoids-Piperine combination was administered 30 min before the probe drug administration. The plasma samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8 and 10h after the probe drug dosing. Plasma samples were also collected 5 and 12 h after flurbiprofen dosing. Following paracetamol dosing all voided urine was collected for 10 h. Individual assays of probe drugs were carried out in both placebo and Curcuminoids-Piperine group. 

Results and Discussion:
  1. The results clearly demonstrate that there is no clinically significant effect of this particular preparation on the pharmacokinetic disposition flurbiprofen, acetaminophen, or midazolam as compared with placebo
  2. These findings suggest that short-term (2 day) treatment with a Curcuminoids/Piperine combination is unlikely to substantially alter the disposition of medications primarily dependent on CYP3A or CYP2C9, or on the UGTs or SULTs responsible for metabolizing
  3. Compared with placebo Curcuminoids-Piperine treatment produced no meaningful changes in plasma Cmax, AUC, clearance, elimination half-life or metabolite levels of the probe drugs

The study shows that the Curcuminoids-Piperine combination is found to be safe and the results indicate that short term use of Piperine-enhanced Curcuminoids preparation is unlikely to result in a clinically significant interaction involving drugs metabolized by CYP3A, CYP2C9 or the paracetamol (acetaminophen) conjugation enzymes. The author further expressed the need for assessing drug interaction potential of nanoparticles of Curcuminoids and other preparations that have been reported to be alternative methods to enhance bioavailability of Curcuminoids.