Pharmacokinetics and partial thromboplastin time after intravenous recombinant hirudin variant-2 in rhesus monkeys.
Abstract
AIM: To study the pharmacokinetics (PK) and changes of kaolin partial
thromboplastin time (KPTT) following single or multiple (7 d) dosing of a novel
recombinant hirudin variant-2 (rHV-2) via the route of iv bolus injection (50 %
of the total dose) plus infusion (the remained 50 % of the dose) in rhesus
monkeys.
METHODS: A crossover design was applied to research the PK and KPTT profiles of
rHV-2 after single (with total dose at 1, 3, and 6 mg/kg, respectively) and
multiple dosing (3 mg/kg). An enzyme-linked immunosorbent assay (ELISA) method
was utilized to determine the level of rHV-2 in plasma.
RESULTS: The concentration profiles of rHV-2 during or after administration were
dependent both on the loading dose and the infusion rate. Mean Cmax after bolus
in three single dose groups were 2.90, 9.78, and 15.68 mg/L, respectively.
Infusions at rate of 8.35, 25, and 50 g/kg/h in 1 h resulted in steady-state
levels of 0.73-0.86, 1.94-2.04, and 5.41-5.59 mg/L, respectively. The plasma
rHV-2 levels during or after administration among doses were significantly
different at most of the time points. Area under concentration-time curve (AUC)
increased linearly with dose but systemic clearances were similar among different
groups. KPTT was significantly prolonged (compared with baseline) at all dose
levels, and trended to increase with dose.
CONCLUSION: Both the loading dose and the infusion rate are very important for
controlling the rHV-2 level, and the data may be helpful for optimizing
dosage-regimen in clinical trials.
Keywords:
thromboplastin time (KPTT) following single or multiple (7 d) dosing of a novel
recombinant hirudin variant-2 (rHV-2) via the route of iv bolus injection (50 %
of the total dose) plus infusion (the remained 50 % of the dose) in rhesus
monkeys.
METHODS: A crossover design was applied to research the PK and KPTT profiles of
rHV-2 after single (with total dose at 1, 3, and 6 mg/kg, respectively) and
multiple dosing (3 mg/kg). An enzyme-linked immunosorbent assay (ELISA) method
was utilized to determine the level of rHV-2 in plasma.
RESULTS: The concentration profiles of rHV-2 during or after administration were
dependent both on the loading dose and the infusion rate. Mean Cmax after bolus
in three single dose groups were 2.90, 9.78, and 15.68 mg/L, respectively.
Infusions at rate of 8.35, 25, and 50 g/kg/h in 1 h resulted in steady-state
levels of 0.73-0.86, 1.94-2.04, and 5.41-5.59 mg/L, respectively. The plasma
rHV-2 levels during or after administration among doses were significantly
different at most of the time points. Area under concentration-time curve (AUC)
increased linearly with dose but systemic clearances were similar among different
groups. KPTT was significantly prolonged (compared with baseline) at all dose
levels, and trended to increase with dose.
CONCLUSION: Both the loading dose and the infusion rate are very important for
controlling the rHV-2 level, and the data may be helpful for optimizing
dosage-regimen in clinical trials.