Enhanced Oral Bioavailability of Domperidone with Piperine in Male Wistar Rats: Involvement of CYP3A1 and P-gp Inhibition

Abstract

-Purpose: Domperidone is a commonly used antiemetic drug. The oral bioavailability of domperidone is very low due to its rapid first pass metabolism in the intestine and liver. Piperine, the main alkaloid present in black pepper has been reported to show inhibitory effects on Cytochrome P-450 (CYP-450) enzymes and P-glycoprotein (P-gp). In the present study we investigated the effect of piperine pretreatment on the intestinal transport and oral bioavailability of domperidone in male Wistar rats. Methods: The intestinal transport of domperidone was evaluated by an in-vitro non-everted sac method and in-situ single pass intestinal perfusion (SPIP) study. The oral pharmacokinetics of domperidone was evaluated by conducting oral bioavailability study in rats. Results: A statistically significant improvement in apparent permeability (Papp) was observed in rats pretreated with piperine compared to the respective control group. The effective permeability (Peff) of domperidone was increased in the ileum of the piperine treated group. Following pretreatment with piperine, the peak plasma concentration (C max ) and area under the concentration-time curve (AUC) were significantly increased. A significant decrease in time to reach maximum plasma concentration (T max ), clearance and elimination rate constant (K el ) was observed in rats pretreated with piperine. Conclusions: Piperine enhanced the oral bioavailability of domperidone by inhibiting CYP3A1 and P-gp in rats. This observation suggests the possibility that the combination of piperine with other CYP3A4 and P-gp dual substrates may also improve bioavailability. Further clinical studies are recommended to verify this drug interaction in human volunteers and patients.

Improved Solubility and Dissolution Rates in Novel Multicomponent Crystals of Piperine with Succinic Acid

“…In addition, piperine has been used to improve cognitive function and as a protective agent against neural degeneration and memory impairment [12]. Furthermore, piperine has been used as a bioenhancer when coadministered with some active pharmaceutical ingredients, such as rapamycin, curcumin, domperidone, and anti-tuberculosis drugs [13][14][15][16]. Unfortunately, the pharmaceutical application of piperine is limited by its low solubility in aqueous medium.…”

Nano‐Cocrystals of Piperine‐Succinic Acid: Physicochemical Characterization and Dissolution Rate Studies

“…[1][2][3][4][5][6] Piperine also shown activity as a bioenhancer, and has the potential to increase the bioavailability of several active pharmaceutical ingredients (API) when administered concurrently, such as rapamycin, curcumin, domperidone, and anti-tuberculosis drugs. [7][8][9][10] Piperine is practically insoluble in water, resulting in poor bioavailability and the limited use of piperine in pharmaceutical preparations. [1,[11][12][13] Based on the Biopharmaceutical Classification System (BCS), piperine is a class II compound (i. e., low water solubility and high permeability).…”

Validation and Quantification of Domperidone in Spiked Plasma Matrix Using Reversed Phase HPLC-UV Method

“…The recommended daily dose is 10-40 mg in divided doses. Domperidone has a low oral bioavailability, approximately 13-17%, due to the extensive first-pass effect and efflux by transporters in the small intestine [1][2][3]. Therefore, the modification or utility of advanced technology of formulation for improving the delivery system of domperidone is demanded.…”