JIN Yong-wen, QIN Hong-yan, RAO Zhi, ZHANG Guo-qiang, MA Yan-rong, WEI Yu-hui, WU Xin-an. Study of pharmacokinetics of digoxin in ovariectomized rats model[J]. Acta Pharm Sin, 2015, 50(12): 1603-1606.
Study of pharmacokinetics of digoxin in ovariectomized rats model
JIN Yong-wen1,2, QIN Hong-yan1, RAO Zhi1, ZHANG Guo-qiang1, MA Yan-rong1,2, WEI Yu-hui1, WU Xin-an1
1. The First Hospital of Lanzhou University, Lanzhou 730000, China; 2. School of Pharmacy, Lanzhou University, Lanzhou 730000, China
Abstract: This study aims to investigate the change of plasma concentration of digoxin(DIG) in rats with ovariectomy. Twelve female SD rats were randomly assigned into ovariectomized group and sham group(n=6). All rats plasma was collected after a single dose of 2 mg·kg-1 DIG administrated orally, serum DIG concentration was determined by LC-MS/MS. The level of P-gp in the intestinal was analyzed by Western blotting. Pharmacokinetic calculations were performed on each individual using DAS 2.0 practical pharmacokinetic software. Compared with the sham group, Cmax of ovariectomized group decreased significantly(P<0.01). There was no significant difference of AUC0-t and the level of P-gp was elevated in ovariectomized group. It was found that Cmax of DIG was significantly reduced after ovariectomy, and the change was associated with the decreased level of estrogen, which contributes to the increased level of P-gp.
Figure 3 Mean plasma concentration-time curves of DIG (2 mg·kg-1) after single administration in rats. n = 6,x± s. P < 0.05,**P < 0.01 vs the sham group
表 1Table 1
Table 1 Pharmacokinetic parameters of DIG in rats. n = 6,x± s. **P < 0.01 vs the sham group
Parameter
OVX
Sham
AUC0-t /ng·mL-1·min-1
58 030 ± 6 819
58 888 ± 9 309
AUC0-∞ /ng·mL-1·min-1
83 473 ± 18 641
96 331 ± 33 414
MRT0-t /min
322 ± 28.29
295 ± 20.88
t1/2z /min
360 ± 105
498 ± 274
tmax /min
40 ± 14.14
38 ± 22.80
CLz/F /L·min-1·kg-1
24.99 ± 4.68
23.20 ± 8.87
Cmax /ng·mL-1
127 ± 22.59**
157 ± 21.10
Table 1 Pharmacokinetic parameters of DIG in rats. n = 6,x± s. **P < 0.01 vs the sham group
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