Clinical Study On Influence Of Pulse-activating Injection On The Pharmacokinetics Of Digoxin In Patiens With Heart Failure

Nowdays the associated medications of PAI and DG in the treatment of HF was more popular and effective, but there was few reports on the reliabilities after the medications. The effect of Pulse-activating injection on the metabolism of digoxin may result in acceleration, postponing or no significant influence. According to limited clinical experiences, the most possible result may be the last, but the other two can't be excluded. To clarify the effect of Pulse-activating injection on digoxin metabolism and to offer a theory basis for reasonable, safety drug application in clinical practice, we carried out the studies (clinical study I and II).In the clinical study I , 40 inpatients, with the cardiac function of level II -III (NYHA), were randomly divided into four groups with delaminations according to age factor: the digoxin group as control group, three trial groups with digoxin plus three different dose of Pulse-activating injection. Comparing with digoxin blood serum concentrations and the pharmacokinetic parameters among all groups at different time, the results suggested that: (1) The blood serum concentration of digoxin in low dose Pulse-activating injection (20ml) group was lower significantly than that in control group (P<0.05), and there were significant difference in preclud half lives (T_1/2), preclud velocity constants (Ke), apparent volume of distribution (Vd), plasma clearanc (CL), drug-time area under the curve (AUC) (P<0.05). (2) Compared with that in control group, the digoxin blood serum concentrations in middle and high dose groups had no significant difference (P>0.05); (3) There were significant difference among the low dose group and middle, high dose groups in digoxin concentrations (P<0.05), while there was no significant difference between the middle group and the high group (P>0.05).In the clinical study II, 40 inpatients, with the cardiac functions of level II -III (NYHA) were randomly divided into four groups with delaminations according to age factor: three trial groups (given three different doses of Pulse-activating injection, respectively 20ml, 40ml, 60ml, n=10). the control group (given equivalence of 5%glucose solution, n=10). Comparing endogenous digoxin-like substance EDLS concentrations among all groups at different time, the results suggested that: (1) EDLS concentration in middle (40ml) and high (60ml) dose groups were significantly higher than that in control group (P<0.05, P<0.01); (2) Compared with that in control group, EDLS concentration in low (20ml) dose group had no significant difference (P>0.05); (3) EDLS concentrations in middle and high dose groups were significantly higher than that in low dose group, and EDLS concentration in high dose group was significantly higher than that in middle dose group (P<0.05).The results suggest that: the matching application of Pulse-activating injection and digoxin in the treatment of congestive heart failure patients, following the improvement of the clinical symptoms simultaneously, could influence digoxin blood serum concentrations and pharmacokinetic parameters somewhat, and could influence the EDLS concentration significantly. The mechanisms of which Pulse-activating injection influence the digoxin metabolism may act by the following ways: (1) Pulse-activating injection may influence the digoxin renal evacuation; (2) It may influence the tissue distributions of digoxin;(3) It may have the functions of stimulating the secretions and releases of EDLS and interference the determined results. But the precise mechanism and its action ways are still to be studied further.