Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

12.2   Pharmacodynamics
After isovolemic exchange of blood with 500 mL of Voluven in healthy volunteers, blood volume is maintained for at least 6 hours.

Pharmacokinetic Properties

12.3   Pharmacokinetics
The pharmacokinetic profile of hydroxyethyl starch is complex and largely dependent on its molar substitution as well as its molecular weight. When administered intravenously, molecules smaller than the renal threshold (60,000-70,000 daltons) are readily and rapidly excreted in the urine, while molecules with higher molecular weights are metabolized by plasma α-amylase prior to excretion via the renal route.

The mean in vivo molecular weight of Voluven in plasma is 70,000 – 80,000 daltons immediately following infusion and remains above the renal threshold throughout the treatment period.

Following intravenous administration of 500 mL Voluven to healthy volunteers, plasma levels of Voluven remain at 75% of peak concentration at 30 minutes post-infusion and decrease to 14% at 6 hours post-infusion. Plasma levels of Voluven return to baseline levels 24 hours following infusion. Plasma clearance, volume of distribution, and elimination half-life of Voluven in healthy volunteers following IV administration of 500 mL were 31.4 mL/min, 5.9 liters, and 12 hours, respectively. Approximately 62 % of Voluven was excreted as hydroxyethyl starch molecules in urine within 72 hours.

The pharmacokinetics of Voluven are similar following single and multiple dose administration. No significant plasma accumulation occurred after daily administration of 500 mL of a 10% solution containing hydroxyethyl starch 130/0.4 over a period of 10 days.
Approximately 70% of Voluven was excreted as hydroxyethyl starch molecules in urine within 72 hours.

Renal Impairment:
Following a single intravenous administration of Voluven (500 mL) in subjects with varying degrees of renal dysfunction, the AUC and clearance of Voluven increased by 73% 
and decreased by 42% in subjects, respectively, with creatinine clearance < 50 mL/min as compared to subjects with creatinine clearance > 50 mL/min. However, terminal half-life and peak hydroxyethyl starch concentration were not affected by renal impairment. Plasma levels of Voluven returned to baseline levels 24 hours following infusion. Approximately 59 % and 51 % of Voluven were excreted as hydroxyethyl starch molecules in urine within 72 hours in subjects with creatinine clearance ≥30 mL/min and <30 mL/min, respectively.

There are no data available on the use of Voluven in subjects undergoing hemodialysis.

Pharmacokinetic data in patients with hepatic insufficiency or in pediatric or geriatric patients are not available. Effects of gender or race on the pharmacokinetics of Voluven have not been studied.