3.3.1 Pharmacokinetics after single-dose trial
The mean serum concentration–time data and PK parameters of EH were
shown in Table 4 and
Figure
3. Following 0.083h infusion, the serum concentration of EH reached a
peak at the end of infusion, and the exposure increased with the
increase of the dose. The half-life(T1/2) of each dose
group changed in the range of 1.7~2.5 h. The Clearance
(Cl) of each dose group changed in the range of
123.9~179.7 mL/h/kg. The apparent volume of distribution
(Vd) changed in the range of 402.7~615.2mL/kg.
The mean serum concentration of EH gradually increased with increasing
dose, and the characteristics of serum concentration-time data in each
dose group were similar. With the increase of the administered dose, the
exposure of hirudin, the active metabolite of EH, in the serum also
gradually increased. The trend of EH plasma concentration was similar to
hirudin, basically showing a linear law. After 7h of EH administration,
the serum hirudin concentration of each dose group was too low to be
detected. The ratio of the area under curve of the hirudin to the EH was
about
2.4-6.3%(Table
5).