Pharmacokinetics of low molecular (monovalent) dextran (Dx 1) in volunteers

Dextran-induced side effects were attributed to preformed antibodies that cross-react with dextran. These antibodies can be blocked by monovalent haptens (dextrans 1) in animals. Dextran 1 is also well tolerated in humans. Plasma levels and renal excretion of monovalent dextran (dextran 1, molecular weight around 1,000) were measured in five volunteers after intravenous administration of 20 ml 15% dextran 1 (3 g), and in one volunteer after intravenous administration of 50 ml (7.5 g). Measurements could be satisfactorily described by a two-compartment open model with elimination from the central compartment only: mean half-life for the beta phase of 1.9 h, a mean cumulative asymptotic elimination of dextran in the urine of 75%, and a mean renal clearance of 137 ml/min with a mean total clearance of 187 ml/min were estimated. The terminal half-life of dextran 60 (Macrodex) was 24 h (median). In volunteers with dextran antibodies no anaphylactoid symptoms were observed after Dx 1. In conclusion, the intravenous preinjection of dextran 1, owing to its pharmacokinetic behavior, should prevent antibody-mediated side effects after infusions with clinical dextrans (e.g., Macrodex, Rheomacrodex).