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      Multiple-Dose Kinetics and Dialyzability of Oxazepam in Renal Insufficiency

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          Abstract

          7 patients with chronic renal insufficiency (4 of whom were on maintenance hemodialysis) and 6 healthy controls received single 15-mg oral doses of oxazepam for 7 consecutive days. Multiple venous blood samples drawn during the 72 h after the final dose were analyzed for concentrations of oxazepam and its glucuronide metabolite, and the extent of oxazepam protein binding. In hemodialysis patients, the final dose was taken just prior to dialysis; arterial (inflow) and venous (outflow) plasma was analyzed as well as dialysate. Mean steady-state plasma concentrations (C<sub>ss</sub>) of total (free and bound) oxazepam in nondialysis renal failure patients (133 ng/ml) were lower, and clearance of total oxazepam (2.5 ml/min/kg) higher, than the corresponding values in controls (330 ng/ml and 1.2 ml/min/kg, respectively). However, these differences were attributable to the greatly increased oxazepam free fraction in renal insufficiency patients (12.0 vs. 4.5% unbound). After correction for individual values of free fraction, C<sub>ss</sub> and clearance of pharmacologically active, unbound oxazepam were essentially identical between groups (14.6 vs. 14.4 ng/ml; 27 vs. 28 ml/min/kg). Compared to controls, C<sub>ss</sub> of the inactive glucuronide metabolite of oxazepam among renal failure patients was greatly increased (2,377 vs. 372 ng/ml) and clearance greatly reduced (0.16 vs. 0.89 ml/min/kg) since excretion of the glucuronide depends on glomerular filtration. Dialyzability of oxazepam and oxazepam glucuronide was minimal. Arterial and venous plasma concentrations were essentially identical, and dialysate concentrations were a small fraction of those in plasma. Thus renal insufficiency does not alter the clearance or C<sub>ss</sub> of pharmacologically active, unbound oxazepam.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1983
          1983
          03 December 2008
          : 34
          : 4
          : 234-238
          Affiliations
          aDivision of Clinical Pharmacology, Tufts-New England Medical Center, Boston, Mass.; bRenal Electrolyte Section, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pa.; cDepartment of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pa., USA
          Article
          183022 Nephron 1983;34:234–238
          10.1159/000183022
          6877459
          © 1983 S. Karger AG, Basel

          Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

          Page count
          Pages: 5
          Categories
          Original Paper

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