3.3.2 Pharmacokinetics after continuous administration trial
The mean serum concentration–time data and PK parameters of EH were
summarized shown in Table 4 and Figure 4. The mean serum concentration
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 in the serum
gradually increased and the trend of EH plasma concentration was similar
to hirudin, basically showing a linear relationship. The hirudin in each
dose group was below the lower limit of quantification after 28h of
continuous administration, and the EH in each dose group was below the
lower limit of quantification after 36h of continuous administration.
The 0.45 mg/kg/h group had no significant accumulation after continuous
administration, and the accumulation ratio AR_Cmax was less than 1.25.
At the doses of 0.15mg/kg/h and 0.30mg/kg/h, the cumulative excretion
rates of EH in urine from the start of administration to 48h after the
end of administration were 4.6% and 9.9% respectively and the
cumulative excretion rates of hirudin were 0.6% and 1.2%(Table 6). The
total cumulative excretion rates of EH plus hirudin were 5.2% and
11.0% respectively, suggesting some other metabolites were produced
from EH.