Chemotherapy
Pharmacology
Pharmacokinetic Evaluation of Imipenem Combined with Cilastatin in Cystic FibrosisBergan T.a · Michalsen H.b · Malmborg A.S.c · Pedersen S.S.e · Pressler T.f · Storrøsten O.T.b · Standvik B.dDepartment of MedicalaMicrobiology, Kaptein W. Wilhelmsen og Frues Bakteriologiske Institut, Rikshospitalet and University of Oslo, and Departments of aMicrobiology and bPediatrics, Aker sykehus, Oslo, Norway; Departments of cMicrobiology and dPediatrics, Huddinge sjukhus, Stockholm, Sweden; Departments of ePaediatrics and fClinical Microbiology, Rigshospitalet, Copenhagen, Denmark
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Article / Publication Details
Published online: September 11, 2009
Issue release date: 1993
Number of Print Pages: 5
Number of Figures: 0
Number of Tables: 0
ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)
For additional information: https://www.karger.com/CHE
Abstract
The pharmacokinetics of imipenem (MK-787) and cilastatin (MK-791) were studied in 30 patients with cystic fibrosis (CF) receiving the drug for therapeutic purposes at doses of 11 mg/kg given as a 30-min infusion. The serum concentrations and urine elimination were studied after the first dose and during steady state. The concentrations were assayed by high-pressure liquid chromatography. The total areas under the imipenem serum concentration curves (AUCs) to infinity were 30.4 ± 6.8 mg-h/1 after the first dose compared with 29.1 ± 7.1 mg-h/1 during steady state (NS). The cilastatin AUCs on the 2 days were 40.3 ± 9.3 and 38.3 ± 0.4 mg-h/1 (NS), respectively. The urinary recovery of imipenem was 47.8 ± 17.8% after the first dose and 57.8 ± 24.2% during steady state (NS). The amounts of cilastatin eliminated in the urine during 6 h were 6/ 7.3 ± 22.9% after the first dose and 60.5 ± 17.0% of the dose during steady state (NS). The mean half-life of imipenem in these CF patients was 1.2 ± 0.4 h on the first day of the examination and within the same range during steady state. The distribution volume (Vdβ) was in the range of 28 liters, the total body clearance was 16.3 liters/h (285 ml/min) on the first day. The t1/2 of cilastatin was 0.59 ± 0.14 h after the first dose and 0.61 ± 0.14 h during steady state. Thus patients with CF eliminated cilastatin more quickly than imipenem.
© 1993 S. Karger AG, Basel
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Article / Publication Details
Published online: September 11, 2009
Issue release date: 1993
Number of Print Pages: 5
Number of Figures: 0
Number of Tables: 0
ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)
For additional information: https://www.karger.com/CHE
Copyright / Drug Dosage / Disclaimer
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.
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