Pharmacokinetics of Bupropion and Its Metabolites in Haemodialysis Patients Who Smoke

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Abstract

To date, no study has investigated the effects of bupropion (BP) in renal-impaired humans. This study aims to identify the pharmacokinetics of BP and metabolites in haemodialysis patients who smoke, determine whether haemodialysis affects BP and metabolite clearance, and suggest the BP dose in haemodialysis. The pharmacokinetics of BP and two of its major metabolites, hydroxybupropion (HB) and threohydrobupropion (TB) were studied in 8 smokers with ESRD receiving haemodialysis. Following a single oral dose of 150 mg bupropion hydrochloride sustained-release, blood samples were taken over 7 days, which were assayed using HPLC-mass spectrometry. Pharmacokinetic analysis was undertaken by non-linear regression using MWPharm. The BP results were similar to those for individuals with normal renal function. The metabolites demonstrated increased areas under the curve, indicating accumulation. Dialysis clearance of HB is unlikely. The results suggest significant accumulation of the metabolites in renal failure. Clarification of the clinical importance of the metabolites and toxic plasma levels is required. The effects of haemodialysis on BP and metabolites require further study. A dose of 150 mg bupropion every 3 days in patients receiving haemodialysis is more appropriate than the current manufacturer’s recommendation (in renal impaired patients) of 150 mg daily. A multi-dose study is required.

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Long-term renal survival in HIV-associated nephropathy with angiotensin-converting enzyme inhibition.

Alice Yam, William C G Burns, B. Williams … (2003)

Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is the most common cause of end-stage renal disease (ESRD) in HIV-infected patients. Angiotensin-converting enzyme (ACE) inhibition has previously shown a short-term benefit in HIVAN. This study examines the long-term effects of ACE inhibition on renal survival in HIVAN. In this single-center prospective cohort study, 44 patients with biopsy-proven HIVAN were enrolled prior to the onset of severe renal insufficiency (serum creatinine or=two antiviral drugs for >or=30 consecutive days, CD4 lymphocyte count, initial median serum creatinine concentration, or proteinuria. Risk of renal failure was reduced with ACE inhibitors (RR = 0.003, P < 0.0001). Exposure to antiretroviral therapy did not have a significant impact on the risk of renal failure. Of the ACE inhibitor-treated group, 87.5% survived compared with 21.4% of the control group (P < 0.001). ACE inhibition initiated prior to severe renal insufficiency may offer long-term renal survival benefits in HIVAN. Diagnosis should be sought early in patients with clinical signs suggestive of HIVAN.

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Single-dose pharmacokinetics of bupropion in adolescents: effects of smoking status and gender.

Mushabbar Syed, M R Simar, Norma J. Stewart … (2001)

Sustained-release (SR) bupropion (Zyban) is approved as a smoking cessation aid for adults. Since smoking often begins in adolescence, we determined the single-dose pharmacokinetics of bupropion SR in 75 adolescent subjects ranging from 13 to 18 years old. Subjects self-reported their smoking status. Urinary cotinine concentration was used to verify smoking status. Thirty-seven subjects (18 males, 19 females) were classified as cigarette smokers and 38 were nonsmokers (19 males, 19 females). Fasted subjects received one tablet (150 mg) of bupropion SR, and plasma samples were collected before (0) and 1/2, 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours after dosing. Plasma samples were analyzed for bupropion and its three major metabolites (hydroxybupropion and the aminoalcohol isomers, erythrohydrobupropion plus threohydrobupropion, expressed as a composite) by solid-phase extraction, followed by LC/MS/MS. Factorial analysis of variance (ANOVA) was used to evaluate the effects of smoking and gender on pharmacokinetic parameters. Smokers and nonsmokers differed significantly (p infinity), volume of distribution (Vd beta) normalized to body weight, maximum plasma concentration (Cmax), and elimination half-life (t1/2 beta) for bupropion were significantly (p infinity and Cmax than males. The mean ratio of hydroxybupropion to bupropion AUC for adolescents was approximately 4 to 5, which is lower than that previously reported for adults. In conclusion, smoking status does not affect the single-dose pharmacokinetics of bupropion SR in adolescents. However, females differ from males in several potentially important PK parameters for bupropion and its major metabolite, hydroxybupropion.

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Author and article information

Journal

Journal ID (publisher-id): NEC

Journal ID (nlm-ta): Nephron Clin Pract

Journal ID (doi): 10.1159/issn.1660-2110

Title: Nephron Clinical Practice

Publisher: S. Karger AG

ISSN (Electronic): 1660-2110

Publication date Subscription-year: 2004

Publication date (Print): July 2004

Publication date (Electronic): 17 November 2004

Volume: 97

Issue: 3

Pages: c83-c89

Affiliations

^aSouthend Hospital NHS Trust, and ^bThe School of Pharmacy, University of London, London, England

Article

Publisher ID: 78635 Other ID: Nephron Clin Pract 2004;97:c83–c89

DOI: 10.1159/000078635

PubMed ID: 15292684

SO-VID: 51f0bdb1-7bf1-43f8-8c08-dd477a841ca3

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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.

History

Date received : 01 March 2003

Date accepted : 28 November 2003

Page count

Figures: 1, Tables: 7, References: 24, Pages: 1

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