Intervention of curcumin on oral pharmacokinetics of daclatasvir in rat: A possible risk for long‐term use

Abstract

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 treatment 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. Pharmacokinetic 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 concomitant 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.

Preventive Effect of Curcumin Against Chemotherapy-Induced Side-Effects

“…The inhibitory effect of curcumin on CYPs and UGTs make it have ability to reduce the degradation of CYP substrates and clearance of UGT substrates. Recent studies also reveal that curcumin can inhibit drug transporters including P-glycoprotein (P-gp), multi-drug resistant associate protein (MRP), breast cancer resistance protein (BCRP), adenosine triphosphate-binding cassette (ABC) such as ABCG1, ABCG2, and ABCB1, organic anion-transporting polypeptide (OATP) such as OATP1B1 and OATP1B3, subsequently resulting in the absorption increase of the above transporter substrates ( Liu et al, 2012 ; Devi et al, 2015 ; Zhou et al, 2017 ; Dogra et al, 2018 ; Wei et al, 2018 ). The above findings demonstrate that curcumin can change pharmacokinetic profile of the enzyme and transporter substrate drugs and increase their plasma levels through the inhibition of these drug-metabolizing enzymes and drug transporters.…”

Effect of IS01957, a para‐coumaric acid derivative on pharmacokinetic modulation of diclofenac through oral route for augmented efficacy

“…It is worth mentioning that we carried out the above mentioned pharmacodynamic and pharmacokinetic studies at equal dose level by taking into consideration that the uses of diclofenac and IS01957 at 1:1 ratio that provide substantial information regarding their pharmacodynamic and pharmacokinetic interaction which are necessary to find out suitability of combination treatment (Nandi et al, ; Sengupta, Nandi, & Pal, ). Further experimentations on dose titration of IS01957, a new bioenhancer for diclofenac will be needed to elucidate maximum improvement in the exposure of diclofenac after oral administration (Dogra et al, ). Further, mechanistic studies for bioenhancement of diclofenac would be beneficial to enumerate the possible pathway of IS01957 to be a novel bioenhancer.…”

Effect of Natural Phenolics on Pharmacokinetic Modulation of Bedaquiline in Rat to Assess the Likelihood of Potential Food–Drug Interaction

“…Even more, information of no interaction between these can be advantageous in terms of safe coadministration. 10 Therefore, there is a need to explore the effect of plant-based natural products on the pharmacokinetics of bedaquiline that can hinder P-gp and CYP3A4. Moreover, people have been extensively consuming plant secondary metabolites/herbs as a dietary supplement/food additive/medicine along with prescription and nonprescription drugs without prior knowledge of their health care providers.…”