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The effects of ferulic acid on the pharmacokinetics of warfarin in rats after biliary drainage.

Li H, Wang Y, Fan R, Lv H, Sun H, Xie H, Tang T, Luo J, Xia Z - Drug Des Devel Ther (2016)

Bottom Line: Comparisons between groups were performed according to the main pharmacokinetic parameters calculated by the DAS 2.1.1 software.The pharmacokinetic parameters showed a significant difference between the WN and WO groups, the WO group showed a decrease of 51% and 41.6% in area under the curve from 0 to time (AUC0- t ) and peak plasma concentration (C max), respectively, whereas time to C max (T max) was delayed 3.27 folds.There were significant differences between the WFO and WFN groups, the WFO group showed a decrease of 63.8% and 70% in AUC0- t and C max, respectively; the delay in T max between the WN and WFN groups (mean, from 132-432 minutes) was significantly different; the mean retention time from 0 to time (MRT0- t ) between the WO and WFO groups (mean, from 718.31-606.13 minutes) also showed a significant difference.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrated Traditional Chinese and Western Medicine, Laboratory of Ethnopharmacology, Xiangya Hospital, Central South University; Department of Pharmacy, Changsha Medical University.

ABSTRACT
According to previous research studies, warfarin can be detected in human bile after oral administration. Ferulic acid (FA) is the main bioactive component of many Chinese herbs for the treatment of cardiovascular disease. To elucidate the effects of FA on the pharmacokinetics of warfarin in rats after biliary drainage is necessary. Twenty rats were randomly divided into four groups: Group 1 (WN): healthy rats after the administration of warfarin sodium, Group 2 (WO): a rat model of biliary drainage after the administration of warfarin sodium, Group 3 (WFN): healthy rats after the administration of warfarin sodium and FA, and Group 4 (WFO): a rat model of biliary drainage after the administration of warfarin sodium and FA. Blood samples were collected at different time points after administration. The concentrations of blood samples were determined by ultraperformance liquid chromatography-tandem mass spectrometry. Comparisons between groups were performed according to the main pharmacokinetic parameters calculated by the DAS 2.1.1 software. The pharmacokinetic parameters showed a significant difference between the WN and WO groups, the WO group showed a decrease of 51% and 41.6% in area under the curve from 0 to time (AUC0- t ) and peak plasma concentration (C max), respectively, whereas time to C max (T max) was delayed 3.27 folds. There were significant differences between the WFO and WFN groups, the WFO group showed a decrease of 63.8% and 70% in AUC0- t and C max, respectively; the delay in T max between the WN and WFN groups (mean, from 132-432 minutes) was significantly different; the mean retention time from 0 to time (MRT0- t ) between the WO and WFO groups (mean, from 718.31-606.13 minutes) also showed a significant difference. Enterohepatic circulation markedly influences the disposition of warfarin in rats, and FA significantly affected the warfarin disposition in rat plasma.

No MeSH data available.


Related in: MedlinePlus

Representative MRM chromatograms of warfarin in rats.Notes: (A) Blank plasma samples from healthy rats; (B) blank plasma samples spiked with warfarin and IS; (C) plasma from rats with biliary drainage after a single administration of warfarin; (D) plasma from healthy rats after a single administration of warfarin; (E) plasma from rats with biliary drainage after the administration of warfarin and ferulic acid; and (F) plasma from healthy rats after the administration of warfarin and ferulic acid.Abbreviations: MRM, multiple-reaction monitoring; ES-TIC, electrospray – total ions chromatograph; IS, internal standard.
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f2-dddt-10-2173: Representative MRM chromatograms of warfarin in rats.Notes: (A) Blank plasma samples from healthy rats; (B) blank plasma samples spiked with warfarin and IS; (C) plasma from rats with biliary drainage after a single administration of warfarin; (D) plasma from healthy rats after a single administration of warfarin; (E) plasma from rats with biliary drainage after the administration of warfarin and ferulic acid; and (F) plasma from healthy rats after the administration of warfarin and ferulic acid.Abbreviations: MRM, multiple-reaction monitoring; ES-TIC, electrospray – total ions chromatograph; IS, internal standard.

Mentions: MRM has high selectivity and accuracy of analysis of chemicals. No interference was observed at the retention times of either warfarin or IS (Figure 2) in plasma samples, which were used for the analysis, and the method exhibited good specificity. Typical MRM chromatograms are shown in Figure 2, and the UPLC-MS/MS spectra of warfarin and methyclothiazide are shown in Figure 3.


The effects of ferulic acid on the pharmacokinetics of warfarin in rats after biliary drainage.

Li H, Wang Y, Fan R, Lv H, Sun H, Xie H, Tang T, Luo J, Xia Z - Drug Des Devel Ther (2016)

Representative MRM chromatograms of warfarin in rats.Notes: (A) Blank plasma samples from healthy rats; (B) blank plasma samples spiked with warfarin and IS; (C) plasma from rats with biliary drainage after a single administration of warfarin; (D) plasma from healthy rats after a single administration of warfarin; (E) plasma from rats with biliary drainage after the administration of warfarin and ferulic acid; and (F) plasma from healthy rats after the administration of warfarin and ferulic acid.Abbreviations: MRM, multiple-reaction monitoring; ES-TIC, electrospray – total ions chromatograph; IS, internal standard.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4940002&req=5

f2-dddt-10-2173: Representative MRM chromatograms of warfarin in rats.Notes: (A) Blank plasma samples from healthy rats; (B) blank plasma samples spiked with warfarin and IS; (C) plasma from rats with biliary drainage after a single administration of warfarin; (D) plasma from healthy rats after a single administration of warfarin; (E) plasma from rats with biliary drainage after the administration of warfarin and ferulic acid; and (F) plasma from healthy rats after the administration of warfarin and ferulic acid.Abbreviations: MRM, multiple-reaction monitoring; ES-TIC, electrospray – total ions chromatograph; IS, internal standard.
Mentions: MRM has high selectivity and accuracy of analysis of chemicals. No interference was observed at the retention times of either warfarin or IS (Figure 2) in plasma samples, which were used for the analysis, and the method exhibited good specificity. Typical MRM chromatograms are shown in Figure 2, and the UPLC-MS/MS spectra of warfarin and methyclothiazide are shown in Figure 3.

Bottom Line: Comparisons between groups were performed according to the main pharmacokinetic parameters calculated by the DAS 2.1.1 software.The pharmacokinetic parameters showed a significant difference between the WN and WO groups, the WO group showed a decrease of 51% and 41.6% in area under the curve from 0 to time (AUC0- t ) and peak plasma concentration (C max), respectively, whereas time to C max (T max) was delayed 3.27 folds.There were significant differences between the WFO and WFN groups, the WFO group showed a decrease of 63.8% and 70% in AUC0- t and C max, respectively; the delay in T max between the WN and WFN groups (mean, from 132-432 minutes) was significantly different; the mean retention time from 0 to time (MRT0- t ) between the WO and WFO groups (mean, from 718.31-606.13 minutes) also showed a significant difference.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrated Traditional Chinese and Western Medicine, Laboratory of Ethnopharmacology, Xiangya Hospital, Central South University; Department of Pharmacy, Changsha Medical University.

ABSTRACT
According to previous research studies, warfarin can be detected in human bile after oral administration. Ferulic acid (FA) is the main bioactive component of many Chinese herbs for the treatment of cardiovascular disease. To elucidate the effects of FA on the pharmacokinetics of warfarin in rats after biliary drainage is necessary. Twenty rats were randomly divided into four groups: Group 1 (WN): healthy rats after the administration of warfarin sodium, Group 2 (WO): a rat model of biliary drainage after the administration of warfarin sodium, Group 3 (WFN): healthy rats after the administration of warfarin sodium and FA, and Group 4 (WFO): a rat model of biliary drainage after the administration of warfarin sodium and FA. Blood samples were collected at different time points after administration. The concentrations of blood samples were determined by ultraperformance liquid chromatography-tandem mass spectrometry. Comparisons between groups were performed according to the main pharmacokinetic parameters calculated by the DAS 2.1.1 software. The pharmacokinetic parameters showed a significant difference between the WN and WO groups, the WO group showed a decrease of 51% and 41.6% in area under the curve from 0 to time (AUC0- t ) and peak plasma concentration (C max), respectively, whereas time to C max (T max) was delayed 3.27 folds. There were significant differences between the WFO and WFN groups, the WFO group showed a decrease of 63.8% and 70% in AUC0- t and C max, respectively; the delay in T max between the WN and WFN groups (mean, from 132-432 minutes) was significantly different; the mean retention time from 0 to time (MRT0- t ) between the WO and WFO groups (mean, from 718.31-606.13 minutes) also showed a significant difference. Enterohepatic circulation markedly influences the disposition of warfarin in rats, and FA significantly affected the warfarin disposition in rat plasma.

No MeSH data available.


Related in: MedlinePlus