Pharmacokinetics of Bupropion and Its Metabolites in Haemodialysis Patients Who Smoke

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.

[1]  R. Foley,et al.  Smoking and cardiovascular outcomes in dialysis patients: the United States Renal Data System Wave 2 study. , 2003, Kidney international.

[2]  H. Berkel,et al.  Single‐Dose Pharmacokinetics of Bupropion in Adolescents: Effects of Smoking Status and Gender , 2001, Journal of clinical pharmacology.

[3]  C. Sánchez,et al.  Comparison of the Effects of Antidepressants and Their Metabolites on Reuptake of Biogenic Amines and on Receptor Binding , 1999, Cellular and Molecular Neurobiology.

[4]  G. Matzke,et al.  Drug prescribing in renal failure: Dosing guidelines for adults , 1999 .

[5]  J. A. Johnston,et al.  Pharmacokinetics of Bupropion and its Metabolites in Cigarette Smokers versus Nonsmokers , 1997, Journal of clinical pharmacology.

[6]  B. Pollock,et al.  Pharmacokinetics of Single‐ and Multiple‐Dose Bupropion in Elderly Patients with Depression , 1995, Journal of clinical pharmacology.

[7]  P. Goodnick.  Pharmacokinetic Optimisation of Therapy with Newer Antidepressants , 1994, Clinical pharmacokinetics.

[8]  A. Storrow.  Bupropion overdose and seizure. , 1994, The American journal of emergency medicine.

[9]  P. Goodnick.  Blood levels and acute response to bupropion. , 1992, The American journal of psychiatry.

[10]  A. Puech,et al.  Antidepressant profile of bupropion and three metabolites in mice. , 1990, Pharmacopsychiatry.

[11]  W. Potter,et al.  Bupropion in depression. II. The role of metabolites in clinical outcome. , 1988, Archives of general psychiatry.

[12]  C. DeVane,et al.  Pharmacokinetics of bupropion and its major basic metabolites in normal subjects after a single dose , 1985, Clinical pharmacology and therapeutics.

[13]  O. Mamer,et al.  Determination of plasma bupropion and its relationship to therapeutic effect. , 1984, Biomedical mass spectrometry.

[14]  S. Preskorn.  Antidepressant response and plasma concentrations of bupropion. , 1983, The Journal of clinical psychiatry.

[15]  Royal College of Physicians , 1897 .

[16]  D. Cameron,et al.  The effect of experimentally-induced renal failure on accumulation of bupropion and its major basic metabolites in plasma and brain of guinea pigs , 2006, Psychopharmacology.

[17]  J. Posner,et al.  Alcohol and bupropion pharmacokinetics in healthy male volunteers , 2004, European Journal of Clinical Pharmacology.

[18]  D. H. Schroeder,et al.  Pharmacokinetics of bupropion, a novel antidepressant agent, following oral administration to healthy subjects , 2004, European Journal of Clinical Pharmacology.

[19]  C. R. Harris,et al.  Fatal bupropion overdose. , 1997, Journal of toxicology. Clinical toxicology.

[20]  S. Preskorn.  Should bupropion dosage be adjusted based upon therapeutic drug monitoring? , 1991, Psychopharmacology bulletin.

[21]  Devane Cl,et al.  Stability of bupropion and its major metabolites in human plasma. , 1985 .

[22]  C. DeVane,et al.  Stability of bupropion and its major metabolites in human plasma. , 1985, Therapeutic drug monitoring.

[23]  D. H. Schroeder,et al.  Clinical pharmacokinetics of bupropion: a review. , 1983, The Journal of clinical psychiatry.

[24]  M Wolfson,et al.  Drug prescribing in renal failure: dosing guidelines for adults. , 1983, American journal of kidney diseases : the official journal of the National Kidney Foundation.