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In vivo distribution of hydrocortisone over whole blood: a novel method for the extraction of erythrocytes
Authors:O Driessen  L Treuren  A Moolenaar  J W Meijer  P Verheijen
Affiliation:Department of Pharmacology, Medical Faculty, University of Leiden, The Netherlands.
Abstract:Ten mg hydrocortisone (HC) was administered intravenously to a healthy volunteer after a dexamethasone suppression test and HC concentrations were determined from 1-270 min in plasma, plasma water and on erythrocytes. HC was extracted from erythrocyte concentrates with high efficiency by HC-poor plasma or by human or bovine albumin solutions. Determination of HC in the plasma of the volunteer mainly gave insight about the concentration time course of HC bound to plasma proteins. One minute after HC injection the amount associated with erythrocytes was about half the amount bound to plasma proteins. Decrease of HC in plasma, and hence on plasma proteins, was monophasic from 30-270 min with a half-life of 116 min. Decrease of HC associated with erythrocytes and HC free in plasma water was biphasic from 30-270 min and initially HC diminished about five times faster from these compartments than from plasma proteins. At the end of the observation period half-lives on plasma proteins, erythrocytes and in plasma water were similar, i.e., at 120 min. It is concluded from these as well as from previous in vitro experiments that erythrocytes gain importance as HC carriers at increasing HC blood concentrations. Once charged, erythrocytes yield HC much more readily than do plasma proteins. This "last come first go" phenomenon of association of HC with erythrocytes is known also to exist for certain drugs. It indicates erythrocytes as important transporters of non-freely in water soluble compounds.
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