The Biological Relevance of the Protein Binding of Diazoxide

: The biological importance of the binding of diazoxide to serum protein was studied in vitro. Contractions in the rings of the rabbit pulmonary artery evoked by electrical field stimulation or exogenous noradrenaline (NA) were studied in the absence and presence of serum albumin (45 g/1) in Krebs–Henseleit (K–H) solutions. Diazoxide concentrations up to 128 μg/ml in the K–H solution and to 256 μg/ml in albumin K–H solutions diminished the contractions and albumin reduced this diminishing effect. Because of an apparent binding of exogenous noradrenaline to albumin only the experiments with electrical field stimulation were used to assess the biological importance of the protein binding of diazoxide. At 2 μg/ml of diazoxide the free drug fraction determined by ultrafiltration was 5% but determined by our biological method the free (active) fraction was 65%. In accordance with a previous clinical study we conclude that the binding of diazoxide to serum protein is important for the transportation of the drug to the arteriolar wall which apparently has a much higher affinity for the drug than serum albumin