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      Pharmacokinetics of Bupropion and Its Metabolites in Haemodialysis Patients Who Smoke

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          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.

          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.

            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.

              Author and article information

              Nephron Clin Pract
              Nephron Clinical Practice
              S. Karger AG
              July 2004
              17 November 2004
              : 97
              : 3
              : c83-c89
              aSouthend Hospital NHS Trust, and bThe School of Pharmacy, University of London, London, England
              78635 Nephron Clin Pract 2004;97:c83–c89
              © 2004 S. Karger AG, Basel

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