Pharmacokinetics of glycerol administered orally in healthy volunteers

Of the three standard osmotherapeutics glycerol, mannitol and sorbitol, glycerol (CAS 56-81-5) alone can be applied orally. As only limited pharmacokinetic data after oral administration are available, studies were performed in 10 healthy subjects (2 female, 8 male, body weight 58-90 kg, age 23-47 years). After 12 h of fasting the subjects drank a single dose of 1.2 g/kg glycerol (Glycerol 85% DAB 9, flavoured with lemon juice). For the first 90 min venous blood was sampled every 15 min, for the following 6.5 h every 30 min. Glycerol serum concentrations were determined by an enzymatic procedure. Intestinal absorption was rapid. Maximum glycerol serum levels ranging from 1285-2238 mg/l (median = 1770 mg/l) were observed 1-2 h after ingestion. On the assumption of full intestinal absorption total body clearance was 0.18-0.26 l/h.kg, and the apparent volume of distribution 0.18-0.34 l/kg. The terminal elimination half-life ranged from 0.61-1.18 h. The concentration-time curves were not adequately described by linear pharmacokinetic models. In all subjects glycerol serum concentrations were high enough to induce increases of serum osmolality of at least 10 mosmol/kg. No signs of haemolysis or haemodilution were observed.