The Effect Of Pepper On The Pharmacokinetics Of Puerarin And Magnolol In Rats

ObjectiveWhite pepper (Piper nigrum L.), known as "the king of spices", is important in our daily diet. Piperine (1-piperoyl piperidine) is an active ingredient in pepper, which had been reported to promote the bioavailability of many drugs.Puerarin is a major active isoflavone isolated from the roots of Pueraria lobata (Willd.) Ohwi. Magnolol is one of the major activity compound of Magnolia officinalis. These efficacy were therapeutically decreased due to poor water-solubility and low oral bioavailability. Co-administration of plant foods with drugs is frequent, and their clinically relevant interactions are increasingly attracting researchers for the sake of public health. It was hypothesized that concurrent intake of puerarin/magnolol and pepper might alter the pharmacokinetic parameters in vivo. This article was to.study these drug interaction and provide theory basis for reasonable combination.Methods1. Used HPLC to establish methods for determination the concentration of drug in biological sampleA Shimadzu HPLC system consisting of pump and UV detector was used for all analyses. The chromatographic resolution of puerarin was carried out on a Diamonsil-C18 column with the isocratic mobile phase (0.2% acetic acid in water and methanol (63:37, v/v)) at a wavelength of 249 nm. The chromatographic resolution of magnolol and piperine was carried out on a Diamonsil-C18 column with the isocratic mobile phase (0.1% acetic acid in water and methanol (22:78, v/v)) at two wavelength of 294 and 340 nm.2. Effect of piperine and pepper on pharmacokinetics of puerarin orally and intravenouslyTo explore the effect of oral piperine and pepper on the oral pharmacokinetics of puerarin, the rats were randomly divided into five groups as follows:(1) control group; (2) low dose of piperine group; (3) high dose of piperine group; (4) low dose of white pepper group. (5) high dose of white pepper group. Right after oral pretreatment, puerarin was administered intragastrically to rats. To study the effect of oral piperine and pepper on the intravenous pharmacokinetics of puerarin, the rats were also randomly divided into five groups. The pretreatment groups were identical to those described above. Thirty minutes after oral pretreatment, puerarin was administered intravenously to rats. Determination of puerarin in plasma samples using the established HPLC method. The pharmacokinetic analysis was performed by The Drug and Statistics software. Comparisons of the pharmacokinetic parameters were analyzed by the two-tailed unpaired Student’s t-test.3. Pharmacokinetics interaction of piperine and magnolol after orally simultaneouslyThe combined group was given magnolol right after oral pretreatment with piperine. The control group was given the corresponding drug by intragastrically. Simultaneous determination of magnolol and piperine in plasma samples using the established HPLC method. The pharmacokinetic analysis was performed by the Drug and Statistics software. Comparisons of the pharmacokinetic parameters were analyzed by the two-tailed unpaired Student’s t-test.Results1. Used HPLC to establish a method for determination the concentration of drug in biological sampleA method has been established for determination the concentration of drug in biological sample, The average relative、calibration curves data、intra- and inter-day precision and accuracy、mean extraction recoveries、stable were measured with QC samples at three concentration levels. The result are meet the demand for analysis. Therefore, the proposed method was applicable to pharmacokinetic studies.2. Effect of piperine and pepper on pharmacokinetics of puerarin orally and intravenouslyUpon concomitant administration with puerarin and piperine, the Cmax and AUC of puerarin was significantly increased, as compared with control group. Tmax of puerarin was decreased gradually with the increase of piperine dose. In contrast, the Cmax and AUC of puerarin co-administrated with white pepper were declined respectively, as compared to control group. Compared with the oral pharmacokinetics of puerarin, the intravenous pharmacokinetics of puerarin was not significantly (P>0.05) affected by pretreatment with piperine. However, the combined use of white pepper with puerarin increased the AUC of puerarin, as compared to the control group. The t1/2 of puerarin was increased and CL was reduced in the presence of white pepper.Overall, these results indicated that the pharmacokinetic profiles of puerarin were changed differently when co-administered with piperine and pepper.3. Pharmacokinetics interaction of piperine and magnolol after orally simultaneouslyAfter concomitant administration with magnolol and piperine, the Cmax and AUC of magnolol was significantly decreased, as compared with control group. However, the combined use of magnolol with piperine did not alter the pharmacokinetics of piperine, as compared to the control group. Although Cmax of piperine was decreased by the high dose of magnolol, the difference in AUC, Vd and t1/2 between groups did not reach statistical significance.ConclusionThe present study suggests that effects of white pepper and piperine on pharmacokinetics of puerarin in rats were significantly different. These findings indicate that the major active component might not reflect the role of the whole natural product in the pharmacokinetics of diet-drug interactions. Piperine has obvious inhibitory effect on the absorption of magnolol after concomitant administration. The pharmacokinetics of piperine did not affected by magnolol after oral administration. Therefore, combined use of piperine or piperine-containing diet with puerarin and magnolol should require careful monitoring for the potential interactions.