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Journal of Chinese Integrative Medicine ›› 2009, Vol. 7 ›› Issue (9): 868-872.doi: 10.3736/jcim20090913

• Original Experimental Research • Previous Articles     Next Articles

Effects of ranitidine on pharmacokinetics of rhein from Dachengqi Decoction in rats after oral administration

Yan-yi Ren, Han-lin Gong, Wen-Fu Tang), Mei-hua Wan, Xi Huang   

  1. Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2009-04-02 Accepted:2009-07-17 Online:2009-09-20 Published:2009-09-15
  • Contact: Wen-Fu Tang E-mail:wftang900@126.com

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Objective

To explore the effects of ranitidine on pharmacokinetics of rhein in rats after oral administration of Dachengqi Decoction (DCQD), a compound traditional Chinese herbal medicine.
Methods

Twelve male Sprague-Dawley rats were divided into DCQD group and DCQD plus ranitidine group, and were orally administered with DCQD at a dose of 10 g/kg or DCQD (10 g/kg) combined with ranitidine (150 mg/kg), respectively. Blood samples were gathered after a series of time intervals. Metabolism of rhein was determined with a reversed-phase high-performance liquid chromatography with internal standard of 1, 8-dihydroxyanthraquinone and the data were analyzed with DAS 2.1 program. The pharmacokinetic parameters were compared between the two groups.
Results

The pharmacokinetic parameters of rhein in the DCQD group, including peak concentration (Cmax), area under the plasma concentration-time curve (AUC), distribution phase half-life (t1/2α), elimination rate constant (K10) and central to peripheral transfer rate constant (K12), were significantly different to those in the DCQD plus ranitidine group (P<0.05, P<0.01). There were no significant differences in the other parameters between the two groups.
Conclusion

Ranitidine can influence the pharmacokinetics of rhein in rats after oral administration of DCQD.

Key words: Dachengqi Decoction, Ranitidine, Rhein, Chromatography, High pressure liquid, Pharmacokinetics, Rats

Figure 1

Chemical structure of rhein"

Figure 2

Typical chromatograms for determination of rhein and 1, 8-dihydroxyanthraquinone in plasma A: Chromatogram of a blank plasma sample; B: Chromatogram of a plasma sample spiked with rhein (peak 1) and internal standard of 1, 8-dihydroxyanthraquinone (peak 2); C: Chromatogram of a plasma sample collected 20 min after oral administration of DCQD and ranitidine; D: Chromatogram of a plasma sample collected 20 min after oral administration of DCQD alone."

Table 1

Intra-day and inter-day accuracy and precision for rhein"

n Concentration (μg/mL) Concentration measured
($\bar{x}$±s, μg/mL)		 Accuracy (%) Average (%) RSD (%) Average (%)
Intra-day 6 0.769 1 0.711 5±0.049 2 92.51 94.09 6.91 5.33
6 3.076 2 2.847 4±0.134 5 92.56 94.09 4.72 5.33
6 15.381 0 14.948 0±0.651 3 97.18 94.09 4.36 5.33
Inter-day 6 0.769 1 0.712 6±0.052 5 92.65 94.42 4.03 5.42
6 3.076 2 2.910 7±0.141 9 94.62 94.42 4.88 5.42
6 15.381 0 14.765 0±0.595 1 96.00 94.42 7.37 5.42

Table 2

Recovery of rhein in rat plasma"

Concentration spiked (μg/mL) n Recovery (Mean, %) Average (%) RSD (%) Average (%)
0.769 1 6 92.66 94.42 7.4 5.4
3.076 2 6 94.62 94.42 4.8 5.4
15.381 6 95.99 94.42 4.0 5.4

Figure 3

Concentration-time curve of rhein in rats Data points represent the mean (n=6)."

Table 3

Pharmacokinetic parameters of rhein in rat plasma"

Parameter ($\bar{x}$±s) DCQD (n=6) DCQD plus ranitidine (n=6) P value
t1/2α (h) 0.49±0.10 0.36±0.05 0.017 7
K10 (/h) 1.60±0.42 1.06±0.29 0.027 1
K12 (/h) 1.28±0.46 2.99±0.79 0.001 0
AUC(0-t) (mg/L·h) 12.25±3.76 6.28±2.27 0.007 7
AUMC(0-t) (mg/L·h2) 44.13±11.52 25.21±9.71 0.011 7
Cmax (mg/L) 6.01±3.59 2.25±1.12 0.034 5
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