Biopharmaceutics and Pharmacokinetics Characterization of Piperine, the Active Component from Black Pepper
Refereed conference paper presented and published in conference proceedings

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Piperine, the biological active component in black pepper, served several pharmacologic actions such as anti-depression, anti- convulsion, anti-carcinoma, anti-oxidation and anti-inflammation. Being such a common condiment in our daily life, the biopharmaceutics and pharmacokinetic characters of piperine have not been thoroughly studied. The present study aims to illustrate the absorption, metabolism and biodistribution of piperine.
The intestinal permeability of piperine was evaluated by Caco-2 monolayer model. During the bi-direction transport study, 20 μM of piperine was loaded in the donor side followed by collecting 100 μl sample from the receiver side and immediate supplement of blank PBS+ buffer. The piperine concentrations in the collected samples were analyzed by LC-MS/MS method.
Biodistribution of piperine was conducted in SD rats (n=5) after oral administration of piperine in saline with 50% PEG-400 at 35 mg/kg. At 6 h post dosing, the rats were sacrificed to obtain blood, adipose tissue, brain, heart, kidney, large intestine, liver, lung, muscle, small intestine, spleen, stomach, testis, urine and feces. The collected blood samples were immediately centrifuged to obtain plasma. Other collected tissues and feces were homogenized with 3 times volume of water containing 0.2% formic acid. Tissue homogenates, plasma and urine were mixed with 3 volumes organic solvent for protein precipitation followed by centrifugation. Piperine concentrations in the supernatants were analyzed by LC-MS/MS method.
To evaluate the metabolism of piperine, in-vivo metabolites in rat plasma, liver, urine, bile and brain samples collected 6 h after oral administration of 35 mg/kg piperine were first screened by LC/Q-TOF/MS. Phase I hepatic metabolism were further evaluated by incubating piperine with 0.5 mg/ml rat liver microsome, NADPH and other co-factors. In addition, the combined phase I and phase II metabolisms were studied by incubating piperine with 2 mg/ml rat liver S9 fraction, NADPH and other co-factors for glucuronidation or sulfation. After 1.5 h of the above incubations, the reactions were stopped by adding 3 times volume of ice-cold organic solvent followed by analyzing the remaining piperine concentrations in the mixture by LC-MS/MS. The metabolic profiles were generated by plotting reaction rate versus piperine substrate concentration and fitted into Michaelis-Menten equation to obtain its enzyme kinetic parameters.
Piperine showed high permeability in bi-directional transport study in Caco-2 monolayer model with Papp values for basolateral to apical and apical to basolateral side to be 5.41 and 4.78 cm/sec, respectively. The efflux ratio of piperine was 1.13, indicating no significant active influx were involved during its absorption.
Piperine was detectable in all the collected tissues with the lowest concentration in urine and highest concentration in stomach and adipose tissue, which account for around 67.08% of total amount of piperine that has been absorbed.
There were four phase I metabolites and seven phase II metabolites identified during the in-vivo metabolites screening. Majority of metabolites assembled in bile and urine with no metabolites found in brain. Reduction, hydroxylation and oxidation are major phase I metabolic pathways for piperine. Phase II metabolites of piperine are formed by further glucuronidation and sulfation of its phase I metabolites. The apparent intrinsic clearance of phase I metabolism was found to be similar to that obtained from combined phase I and glucuronidation or sulfation metabolisms. After further converting the combined Clint into separated phase I and phase II metabolism, it was found that Clint of phase I metabolism were lower than that from glucuronidation or sulfation.
Piperine is a highly permeable drug that could be efficiently absorbed with no extensive hepatic metabolism after oral administration. It could distribute throughout the body and accumulation mainly in adipose tissue due to its high lipophilicity.
All Author(s) ListRen Tianjing, LI Chenrui, WANG Qian, ZHANG Yufeng, ZUO Zhong
Name of Conference2017 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition
Start Date of Conference12/11/2017
End Date of Conference15/11/2017
Place of ConferenceSan Diego, CA
Country/Region of ConferenceUnited States of America
LanguagesEnglish-United States

Last updated on 2018-02-10 at 09:39