Impact of Concomitantly Administered Curcumin on Pharmacokinetics of Daclatasvir in Mice Under the Frame of Herb-Drug Interaction

Abstract:

Objective: Daclatasvir is a new orally acting antiviral drug for the treatment of hepatitis C virus (HCV). It is substrate of both P-glycoprotein (P-gp) and CYP3A4 which are involved in the major pharmacokinetic interaction between drug-drug or drug-food. Curcumin, a natural polyphenol extracted from Curcuma longa is used regularly and widely as food additive or dietary supplement. We surmised that curcumin may interfere with the pharmacokinetics of daclatasvir as curcumin is known to have potential to hinder the drug transporters and hepatic drug metabolising enzymes. Hence, investigations were taken up to assess for such possible interactions. Materials and Methods: Pharmacokinetics of daclatasvir after oral administration as alone and in combination with curcumin (2.5 or 5 or 10 mg/kg) were investigated in Balb/C mice following determination of daclatasvir plasma concentration by using a sensitive LC-MS/MS method. Results: Area under the plasma concentration-time curve for daclatasvir was decreased at lowest dose and increased subsequently at higher doses upon concomitant administration of curcumin with daclatasvir in comparison to daclatasvir alone. Maximum plasma concentration of daclatasvir was enhanced only at highest dose. Overall effects of curcumin on daclatasvir pharmacokinetics were not statistically significant at all dose levels except significant increase in mean residence time. Conclusion: Intensity of curcumin effect on the daclatasvir pharmacokinetics at the experimental dose level in the mice model suggests that dose adjustment is unlikely to be required. Further experimentations are needed to confirm its clinical significance.