Effects of Shenmai injection on serum concentration and pharmacokinetics of digoxin in dogs with heart failure

Objective: To explore the effects of Shenmai Injection (SMI), a compound traditional Chinese herbal medicine, on pharmacokinetics and serum concentration of digoxin when applied together with digoxin. Methods: Twenty dogs with heart failure were randomly divided into 4 groups: control group and low-, medium- and high-dose SMI groups, with 5 dogs in each group. After intravenous injection of digoxin injection at a dose of 7.41 μg/kg, dogs in the control group were administered intravenously with normal saline 20 mL daily for 5 d, and the other groups were intravenously administered with SMI at the doses of 0.517, 1.034 and 1.551 mL/kg respectively. After the administration, the blood was collected at designed time points. Serum concentration of digoxin was determined by high-performance liquid chromatography with electrospray tandem mass spectrometry (HPLC/MS/MS). Results: The low-, medium- and high-dose SMI showed different effects on the pharmacokinetics of digoxin: the low-, medium- and high-dose SMI revealed a tendency to decrease the elimination half-life (T 1/2β) of digoxin. The low-dose SMI showed a tendency to decrease the digoxin concentration. Serum clearance (CL) in the low-dose SMI group was higher than that in the control, and also significantly higher than those in the medium- and high-dose SMI groups (P < 0.05). The area under concentration-time curve (AUC0→∞) in the low-dose SMI group was lower than that in the control group (P = 0.05); the AUC 0→72 h and AUC0→∞ in the low-dose SMI group were significantly lower than those in the medium- and high-dose SMI groups. Low-dose SMI accelerated the clearance of digoxin in blood. Conclusion: Low-, medium- and high-dose SMI shows different effects on pharmacokinetics of digoxin and reveals a tendency to shorten T1/2β of digoxin. Low-dose SMI can accelerate the clearance of digoxin in blood.