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      Pharmacokinetics of Transperitoneal Insulin Transport

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          Abstract

          Seven type I insulin-dependent diabetic patients on continuous ambulatory peritoneal dialysis treatment were selected for this study. Each patient participated in three different 6-hour ‘single-dwell’ studies on 3 consecutive days. A mean dose of 33 ± 1.3 U Insulin Actrapid Human was given intraperitoneally each day. The procedures for intraperitoneal insulin administration were: (1) with 1,000 ml Ringer lactate; (2) with 1,000 ml 3.86% glucose-containing dialysate, and (3) into an empty peritoneal cavity. The calculation of the intraperitoneal volume was done with a single injection indicator dilution technique in which 100 kB<sub>q</sub> radioiodinated serum albumin (RISA) was added into the fluid prior to instillation. Free insulin and glucose were analyzed at 16 time intervals in blood and in dialysate during each dwell. After drainage the peritoneal cavity was rinsed with 1,000 ml Ringer lactate followed by two consecutive 5-hour exchanges with 2,000 ml glucose-containing dialysate. Recovery of insulin and RISA was measured in rinsing fluid and in sampled dialysate during the 6-hour dwell. The kinetic calculations made for insulin were disappearance rate (mU/min) from the peritoneal cavity, and appearance rate in circulating blood. After drainage and rinsing, 66.0 ± 10 and 71.8 ± 9.8% of the insulin instilled had disappeared after 6 h from the glucose fluid and from the Ringer solution respectively and did not differ significantly. However, the estimated disappearance rate from the peritoneal cavity was significantly higher in Ringer than in glucose from the time interval 120 to 360 min. A high and peak-shaped insulin concentration in the plasma was found following insulin injection into an empty peritoneal cavity, and was significantly higher than when insulin was dissolved in a 1,000-ml fluid volume. However, a higher blood concentration was also found when Ringer was instilled than when a hyperosmolal glucose solution was instilled. A high first-pass elimination in the liver is suggested. In conclusion, fluid volume and also the osmolality of the solution in the peritoneal cavity decreases the transport rate, but not the bioavailability of insulin given intraperitoneally. Both a high peak shape and a continuous insulin appearance in blood can be achieved. It is suggested that there is a high first-pass elimination of insulin during absorption from the peritoneal cavity. However, the values are uncertain and extended investigations must be done.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1996
          1996
          24 December 2008
          : 74
          : 2
          : 283
          Affiliations
          aDepartment of Nephrology and Endocrinology, University Hospital and Institute of Biophysics, University of Trondheim, Norway; bGambro AB, Lund, cDepartment of Nephrology, University Hospital, Lund, and dDepartment of Nephrology, Kärnsjukhuset, Skövde, Sweden
          Article
          189322 Nephron 1996;74:283-290
          10.1159/000189322
          8893142
          © 1996 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: 8
          Categories
          Original Paper

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