Pharmacokinetics of Bupropion and Its Metabolites in Haemodialysis Patients Who Smoke

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.

Smoking

“…Among 1105 patients with type 1 diabetes and normal urine albumin excretion at baseline, a 4.3-fold greater rate of GFR decline (measured by [125] -iothalamate clearance) was observed in active versus nonactive smokers (Ϫ0.77 versus Ϫ0.18 ml/min per 1.73 m 2 /yr). Additional data were provided by a prospective observational study involving 227 white patients with type 2 diabetes and nephropathy (30).…”

“…A cautious approach is particularly necessary in situations in which the nicotine-related increase in sympathetic activity may have deleterious effects; however, it cannot be expected that NRT is more injurious than continuous smoking. Concerning therapy with bupropion, a dosage reduction in patients with ESRD has been suggested because of significant accumulation of two major active metabolites (125). Before more information is available, a dosage of 150 mg of bupropion, orally, every 3 d in patients who are on renal replacement therapy seems appropriate (125).…”

“…Concerning therapy with bupropion, a dosage reduction in patients with ESRD has been suggested because of significant accumulation of two major active metabolites (125). Before more information is available, a dosage of 150 mg of bupropion, orally, every 3 d in patients who are on renal replacement therapy seems appropriate (125). Concerns that bupropion may increase suicide risk are unproved (126).…”

Hemodialysis Treatment of Monomorphic Ventricular Tachycardia Associated with Chronic Lithium Toxicity

“…In renal failure, hydroxybupropion has a half-life >30 h [13]. The levels were drawn 12 h after admission and still would have been less than therapeutic if drawn immediately upon admission.…”

Simultaneous Quantitative Determination of Bupropion and its Metabolites by High Performance Liquid Chromatography Tandem Mass Spectrometry Detection: Application to Bioequivalence Study

“…Reported C max based on Bupropion hydrochloride 100 mg tablets for BPR, HBPR and THBPR are 136.2 ng/ml, 269.0 ng/ml and 88.8 ng/ml, respectively. Literature reveals that HPLC methods for plasma, [1][2][3][4] stability method for plasma, 5 metabolite characterization, [6][7] LC-MS methods for human plasma [8][9][10][11][12][13] and rat plasma, 14 pharmacokinetics analysis in human or rat plasma [15][16][17][18][19][20][21][22][23][24] for bupropion and/its metabolite(s) and LC-MS methods for bupropion with combination [25][26][27] are reported. It is noted that reported HPLC methods are not sensitive for the quantification in terminal plasma concentration of bupropion and/or metabolites.…”