RESEARCH ARTICLE Intervention of curcumin on oral pharmacokinetics of daclatasvir in rat: A possible risk for long‐term use Ashish Dogra 1,2 | Shipra Bhatt 1,2 | Asmita Magotra 1,2 | Anjna Sharma 1,2 | Pankul Kotwal 1,2 | Abhishek Gour 1,2 | Priya Wazir 1 | Gurdarshan Singh 1,2 | Utpal Nandi 1,2 1 PK‐PD, Toxicology and Formulation Division, CSIR‐Indian Institute of Integrative Medicine, Jammu, India 2 Academy of Scientific and Innovative Research (AcSIR), CSIR‐Indian Institute of Integrative Medicine, Jammu, India Correspondence Utpal Nandi, PK‐PD, Toxicology and Formulation Division, CSIR‐Indian Institute of Integrative Medicine, Jammu, J&K 180 001, India. Email: unandi@iiim.ac.in; utpalju@gmail.com Funding information Council of Scientific and Industrial Research, Grant/Award Number: MLP6006 Curcumin, a natural diarylheptanoid, is extensively used as a food additive or dietary supplement on the regular basis. It is known to have potential to encumber the drug transporters and hepatic drug metabolizing enzymes that lead to pharmacokinetic interactions with drug or food. Daclatasvir is a new orally acting drug for the treat- ment of chronic Hepatitis C Virus infections. This is a substrate of P‐glycoprotein and CYP3A4 that are involved in the major pharmacokinetic interaction. Hence, the studies' aim is to assess for any possible pharmacokinetic interactions. Pharmacoki- netic studies of daclatasvir in presence or absence of curcumin were carried out in Wistar rats following oral administration. Parallelly, the oral pharmacokinetics of daclatasvir was also determined in the presence of ketoconazole or quinidine. Studies revealed that plasma level of daclatasvir was not altered significantly during concom- itant single dose administration of curcumin, whereas significantly decreased upon pretreatment for 7 days with curcumin at high dose level. Ketoconazole and quinidine markedly increase daclatasvir exposure following concomitant administration with daclatasvir. It can be concluded that dose adjustment is unlikely to be required for intermittent use of curcumin at low dose but cautious for chronic and concomitant use of curcumin at a high dose. KEYWORDS curcumin, daclatasvir, food–drug interaction, herb–drug interaction, pharmacokinetics 1 | INTRODUCTION Daclatasvir, a new antiviral agent, is the first‐ever approved NS5A rep- lication complex inhibitor of Hepatitis C Virus (Soriano et al., 2017). According to the recent report of American Association for the Study of Liver Diseases, daclatasvir (60 mg) in combination with sofosbuvir (400 mg) is recommended as first‐line therapy in patients with Geno- type 3 without cirrhosis (Manolakopoulos, Zacharakis, Zissis, & Giannakopoulos, 2016). This is given orally in its hydrochloride salt form and having the oral bioavailability of 67% (Bifano et al., 2015; Hussar & Friedman, 2016). Being a substrate of P‐glycoprotein (P‐ gp) and metabolized via Cytochrome‐450 3A4 (CYP3A4) isoenzymes, dose adjustments are frequently necessary when daclatasvir is coadministered with other strong inducer or inhibitor of these trans- porters or enzymes (Manolakopoulos et al., 2016). Curcumin is extracted from Curcuma longa, commonly known as turmeric. It is used as food additive or dietary supplement. It has numerous pharmacological activities for clinical use. It inhibits both P‐gp and CYP isoenzymes that are key for drug–drug or drug–food interactions as these are taken inadvertently and frequently with Abbreviations: AUC 0‐∞ , Area under the curve for plasma concentration from zero to infinity; AUC 0‐t , Area under the curve for plasma concentration from zero to the last measurable plasma sample time; Cl/F, Clearance following oral administration; C max , Maximum plasma concentration; CYP, Cytochrome‐450; ESI, Electro spray ionization; IS, Internal standard; LC–MS/MS, Liquid chromatography tandem mass spectrometry; MRM, Multiple reaction monitoring; OATP, Organic anion transporting polypeptide; P‐gp, P‐ glycoprotein; SEM, Standard error mean; T 1/2 , Elimination half‐life; T max , Time to reach maximum plasma concentration Received: 27 December 2017 Revised: 3 April 2018 Accepted: 2 May 2018 DOI: 10.1002/ptr.6123 Phytotherapy Research. 2018;32:1967–1974. Copyright © 2018 John Wiley & Sons, Ltd. wileyonlinelibrary.com/journal/ptr 1967