Elopment and Therapy 2013:DovepressDovepressPharmacokinetics of glycyrrhizic acid diethyl esterA GZDE concentration ( /mL)3,B GZ concentration ( /mL)0 two four six eight 10 800 700 600 500 400 300 200 one hundred 0 0 two four 6 82,Time (hour)Time (hour)Figure two Bile gZDe (A) and gZ (B) concentration versus time profiles following intravenous administration of GZDE (GZ dose two mg per rat). The information represent the imply of three experiments. standard deviation bars are shown with each and every symbol. Abbreviations: gZ, glycyrrhizic acid; gZDe, glycyrrhizic acid diethyl ester.1 hour and 8 hours immediately after administration was 68.5 and 72.6 from the administered dose, respectively. Alternatively, the presence of GZ became clear from determination of GZ in bile by HPLC. It was confirmed that GZ did not exist inside the GZDE formulation ahead of administration. Hence, the result indicates that GZDE was changed to GZ in rats soon after administration. In the concentrationtime profile for GZ in bile, speedy elimination (at 0.5 hours) and moderate elimination (two hours) of GZ were observed. The GZ concentration in bile at 30 minutes soon after administration was 684 /mL, suggesting that conversion from GZDE to GZ occurred quickly.2448268-14-0 supplier Elimination of GZ to bile at 30 minutes and two and eight hours was 12.three , 16.6 , and 19.4 with the administered GZ dose (2 mg), respectively. The sum of GZDE and GZ elimination into bile at 8 hours was 92.0 with the administered dose. Namely, the ratio of GZDE to GZ in bile was approximately four:1 immediately after intravenous administration.Table 1 Pharmacokinetic parameters for gZDe and gZ after intravenous administration of gZDe (gZ dose 2 mg per rat)Parameter A ( /ml) (per hour) B ( /ml) (per hour) t1/2 (hours) aUc ( h/ml) CLtotal (ml/hour) GZDE 28,964 1342 4.56 0.36 37.five two.6 0.245 0.042 2.63 0.23 six,502 428 0.26 0.03 GZ three,470 425 3.35 0.33 36.0 2.7 0.148 0.022 4.68 0.46 1,278 142 1.56 0.It has been reported that virtually all GZ is quickly excreted into bile by means of the liver soon after intravenous or subcutaneous administration. Particularly, 85 on the administered GZ dose (5 mg/kg) in rats was excreted into bile more than four hours;11 93.three of the administered GZ dose (four mg per rat) was excreted into bile till 8 hours;8 and 80.six with the administered GZ dose (one hundred mg/kg) in rats have been excreted into bile until 48 hours.12 Comparison of those reports indicates that about 20 with the GZDE administered is converted into GZ, that is then excreted rapidly into bile. Further, it is actually intriguing that each apparent elimination rate constants ( and ) for GZDE shown in Table 1 (four.439579-12-1 site 56 per hour and 0.PMID:24179643 245 per hour) have been greater than these for GZ (three.35 per hour and 0.148 per hour). From these final results, it truly is recommended that the efflux rate of GZDE into bile by efflux transporters in the liver, like multidrug resistance protein two, may perhaps be high in comparison using the efflux price of GZ into bile. GZ is one of the substrates of multidrug resistance protein 2 in the liver,13,14 and also the initial elimination price continuous for GZDE (4.56 per hour) was remarkably higher compared with that for GZ (1.99 per hour) right after intravenous administration of GZ in rats.15 For that reason, it was predicted that the efflux price of GZDE from liver to bile would be fast as compared using the conversion price from GZDE to GZ following intravenous administration of GZDE.Note: The data represent the mean standard deviation of 3 experiments. Abbreviations: gZ, glycyrrhizic acid; gZDe, glycyrrhizic acid diethyl ester; aUc, location beneath the concentrat.