Format

Send to

Choose Destination
J Pharm Biomed Anal. 2016 Sep 5;128:286-293. doi: 10.1016/j.jpba.2016.05.041. Epub 2016 May 24.

Non-linear pharmacokinetics of piperine and its herb-drug interactions with docetaxel in Sprague-Dawley rats.

Author information

1
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region; Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, China.
2
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region.
3
State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, Macau.
4
Center for Advanced Drug Research and Evaluation, College of Pharmacy, Western University of Health Sciences, USA.
5
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region. Electronic address: joanzuo@cuhk.edu.hk.

Abstract

Piperine (PIP), the major alkaloid component from Piper longum L. and Piper nigrum L., could enhance the bioavailabilities of other drugs including rosuvastatin, peurarin and docetaxel (DOX) via inhibition of CYP3A and P-glycoprotein activity. Nevertheless, the effect of such drug combination usage on the in vivo exposure of PIP has not been investigated due to lack of assay for the simultaneous determination of PIP and other drugs such as DOX. Besides, the reported pharmacokinetics of PIP varied a lot without appropriate bioavailability determined from the same dose. In the current study, an LC/MS/MS method has been developed to simultaneously determine the plasma concentrations of PIP and DOX and further applied to investigate the pharmacokinetics properties of PIP after oral and intravenous administrations as well as the pharmacokinetics interactions between PIP and DOX after their co-administration. A simple protein precipitation method was employed for plasma sample treatment by adding a mixture of methanol and acetonitrile (1:1, v/v) with glibenclamide as internal standard (IS). The LC/MS/MS system consisted of Agilent 6430 series LC pumps and auto-sampler. The chromatographic separation was carried out in 15min on a Waters C18 column (150×3.9mm i.d., 4μm) with a mobile phase containing 0.2% formic acid and acetonitrile (1:1, v/v) at a flow rate of 0.4ml/min. The detection was performed using the positive ion electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode with precursor-to-product ion transitions at m/z 286.1→201.1 for PIP, m/z 830.3→548.9 for DOX and m/z 494.2→369.0 for IS. The method demonstrated good linearity for both PIP and DOX over the concentration range of 2.5-1280ng/ml with LLOD at 2.5ng/ml. The intra-day and inter-day precisions were less than 13.34% and relative error (R.E.) representing accuracy was in the range of -11.38 to 3.15%. The recoveries of PIP, DOX and IS were above 75% and there was no matrix effect. PIP and DOX exhibited good stabilities under various conditions. PIP was administrated via intravenous bolus at 3.5mg/kg and via oral administration at 35mg/kg and 3.5mg/kg, while DOX was intravenously administrated at 7mg/kg to Sprague-Daley rats. The plasma concentrations of PIP and DOX were determined using the above developed and validated method. At the dose of 3.5mg/kg, the bioavailability of PIP was calculated to be 25.36%. Its AUC0→t was unproportionally increased with doses, indicating a potential non-linear pharmacokinetics profile of PIP. It was found that the AUC0→t and C0 of DOX and t1/2 of PIP were significantly increased after their combination use, suggesting potential enhanced bioavailability of not only DOX but also PIP, which may lead to the overall enhanced pharmacological effects.

KEYWORDS:

Docetaxel; Herb-drug interactions; LC/MS/MS; Pharmacokinetics; Piperine

PMID:
27288758
DOI:
10.1016/j.jpba.2016.05.041
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center