[The in vivo molecular weight and renal threshold of hydroxyethyl starch in the example of molar substituted HES70/0/5]

Abstract

The intravascular changes of the in vivo molecular weight of HES 70/0.5 were investigated on healthy volunteers. A repeated daily infusion of 835 ml of 6% HES solution (50 g HES 70/0.5; Rheohes) during four hours on five consecutive days was performed. The analysis of the distribution of the molecular masses in serum and urine was performed by SEC-HPLC with MALLS/RI detection. The in vivo average molecular weight (Mw) of HES was found to be 58,000 Da at the end of the infusion. This was lower than the Mw of 66,000 Da as measured initially in the HES solution. In the time following the infusion Mw increased steadily up to 64,000 Da because of renal elimination of low molecular HES. However, in the morning before the start of the next infusion of HES, the average molecular weight Mw of HES was even higher up to 71,000 Da. In the first collected portion of urine (i.e. up to 8 h after beginning the infusion) the average molecular weight of HES was as low as 17,000 Da. During the next hours (i.e. in the second collection period lasting from 8 up to 24 h after start of the HES infusion) Mw of HES increased up to 28,000 Da. The top fraction of the first period showed molecular masses of 27,000 Da, in the second collection period top fraction of molecular masses measured 40,000 Da. According to the presented data it is concluded that the renal threshold for medium substituted HES is independent of the initial Mw and related primarily to the molar substitution of the HES used. This renal threshold for medium substituted HES is determined to be at 40,000 Da. The in vivo Mw of HES is variable and related to the sampling time and predicted predominantly by the molar substitution of the HES used. The in vivo Mw, therefore, is not suited for characterisation of HES.