Low blood-to-cerebrospinal fluid passage of sorbitol after intravenous infusion

Compared with mannitol, the osmotherapeutic agent sorbitol is less prone to accumulate in the blood and the same quantity may be infused in a smaller volume. Because of these advantageous characteristics, we studied the pharmacokinetics of sorbitol in serum and cerebrospinal fluid. Six patients (five women and one man; age range, 46-70 years) with an external ventriculostomy and suffering from brain edema due to cerebrovascular disease received sorbitol as part of their therapy. Before and after the first dose of 50 g infused over 20 minutes, sorbitol concentrations in serum and cerebrospinal fluid were determined repeatedly using an enzymatic procedure. Maximal sorbitol concentrations ranged from 2,705 to 5,821 (median, 3,227) mg/l in serum compared with 6.7-130.7 (median, 19.5) mg/l in cerebrospinal fluid. Cerebrospinal fluid maxima were observed 0.17-3 hours after the end of the infusion. Sorbitol elimination in serum was adequately described by a two-compartment pharmacokinetic model (distribution half-life, 0.05-0.14 hour; elimination half-life, 0.23-0.61 hour). Elimination in cerebrospinal fluid followed a single-exponential decay and was considerably slower than that in serum (half-life, 1.3-7.7 hours). The maximal cerebrospinal fluid concentration/maximal serum concentration ratio was low for sorbitol, thus suggesting a small potential risk of inducing an increase of intracranial pressure after osmotherapy (rebound effect).