PHARMACOKINETICS OF LOW-MOLECULAR (MONO-VALENT) DEXTRAN (DX-1) IN VOLUNTEERS

Abstract

Dextran(Dx)-induced side effects were attributed to preformed antibodies that crossreact with Dx. These antibodies can be blocked by monovalent haptens (Dx 1) in animals. Dx 1 is also well tolerated in humans. Plasma levels and renal excretion of monovalent Dx 1 (MW .apprx. 1000) were measured in 5 volunteers after i.v. administration of 20 ml 15% Dx 1 (3 g), and in 1 volunteer after i.v. administration of 50 ml (7.5 g). Measurements could be satisfactorily described by a 2-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 Dx in the urine of 75%, and mean renal clearance of 137 ml/min with a mean total clearance of 187 ml/min were estimated. The terminal half-life of Dx 60 (Macrodex) was 42 h (median). In volunteers with Dx antibodies no anaphylactoid symptoms were observed after Dx 1. The i.v. preinjection of Dx 1, owing to its pharmacokinetic behavior, should prevent antibody-mediated side-effects after infusions with clinical Dx (e.g., Macrodex, Rheomacrodex).