Effects of piperine on the intestinal permeability and pharmacokinetics of linarin in rats.
Although linarin possesses diverse pharmacological activities, its poor oral bioavailability has been a concern for further development. The present study aimed to demonstrate the feasibility of improving the oral absorption of linarin in rats with a bioenhancer‒piperine. First, the intestinal permeability of linarin in the presence and absence of verapamil or piperine was investigated using an in situ single-pass rat intestinal perfusion method. A significant increase in the Peff when co-perfused with verapamil or piperine indicated that piperine effectively inhibited P-glycoprotein mediated efflux of linarin. Then, the pharmacokinetic profiles of linarin in rats after oral administration of linarin (50 mg/kg) alone and in combination with piperine (20 mg/kg) were determined using a validated LC-MS/MS method. The results showed that piperine increased the plasma exposure (AUC) of linarin by 381% along with an increase in the Cmax by 346% and the Tmax from 0.05 h to 0.2 h. The present study revealed that piperine significantly enhanced the oral absorption of linarin in rats by inhibiting P-glycoprotein mediated cellular efflux during the intestinal absorption and likely simultaneously by inhibiting the metabolism of linarin.
School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. fengxinchi19880211@163.com.
Xinchi
X
Feng
School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. yp-liu@163.com.
Youping
Y
Liu
School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. wangxin68k@163.com.
Xin
X
Wang
School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. dixin63@hotmail.com.
Xin
X
Di
D000284:Administration, Oral; D000470:Alkaloids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D052117:Benzodioxoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D006027:Glycosides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D053719:Tandem Mass Spectrometry
D000470:Alkaloids; D052117:Benzodioxoles; D006027:Glycosides; D010880:Piperidines; D053284:Polyunsaturated Alkamides; C008282:linarin; C008922:piperine