Relationship between drug exposure and the efficacy and safety of bupropion sustained release for smoking cessation

Johnston, J. Andrew; Fiedler‐Kelly, Jill; Glover, Elbert D.; Sachs, David P.L.; Grasela, Thaddeus H.; DeVeaugh-Geiss, Joseph

doi:10.1080/14622200110042852

Cited by 76 publications

(47 citation statements)

References 10 publications

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“…The increased hydroxylation of bupropion with significant reduction in bupropion plasma concentration by metamizole seen in our study may reduce the clinical effects by bupropion since the pharmacological activity of hydroxybupropion is about half that of bupropion [16]. Still, it is uncertain to what degree the efficacy of bupropion may be influenced by metamizole due to the pharmacodynamic variability of bupropion [17,18].…”

Section: Discussionmentioning

confidence: 74%

Rapid clinical induction of bupropion hydroxylation by metamizole in healthy Chinese men

Qin

Zhang

Liu

et al. 2012

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Bupropion, an antidepressant and smoking cessation drug, is metabolized to its active metabolite, 4-hydroxybupropion, almost exclusively by CYP2B6.• Metamizole, a pyrazolone derivative with analgesic properties, was shown in an in vitro study to increase significantly the expression of CYP2B6 and bupropion hydroxylase activity.• The effect of metamizole on bupropion hydroxylation has not been investigated and drug interactions may occur between metamizole and bupropion. WHAT THIS PAPER ADDS• Oral administration of metamizole for 4 days significantly altered the pharmacokinetics of both bupropion and its active metabolite, 4-hydroxybupropion, and significantly increased the CYP2B6-catalyzed bupropion hydroxylation in all of the subjects.• Dosage adjustment of bupropion may be needed in patients when metamizole is concomitantly administered. AIMSThis study aimed to investigate the effect of metamizole on bupropion hydroxylation related to different CYP2B6 genotype groups in healthy volunteers. METHODSSixteen healthy male volunteers (6 CYP2B6*1/*1, 6 CYP2B6*1/*6 and 4 CYP2B6*6/*6) received orally administered bupropion alone and during daily treatment with metamizole 1500 mg day -1 (500 mg tablet taken three times daily) for 4 days. Serial blood samples were obtained up to 48 h after each bupropion dose. RESULTSAfter metamizole treatment relative to bupropion alone, the geometric mean ratios (GMRs) and 90% confidence interval (CI) of the AUC(0,•) ratio of 4-hydroxybupropion over bupropion were 1.99 (1.57, 2.55) for the CYP2B6*1/*1 group, 2.15 (1.53, 3.05) for the CYP2B6*1/*6 group and 1.86 (1.36, 2.57) for the CYP2B6*6/*6 group. The GMRs and 90% CI of bupropion were 0.695 (0.622, 0.774) for AUC(0,•) and 0.400 (0.353, 0.449) for Cmax, respectively. The corresponding values for 4-hydroxybupropion were 1.43 (1.28, 1.53) and 2.63 (2.07, 2.92). The t1/2 value was significantly increased for bupropion and decreased for 4-hydroxybupropion. The tmax values of bupropion and 4-hydroxybupropion were both significantly decreased. The mean percentage changes in pharmacokinetic parameters among the CYP2B6 genotype groups were not significantly different. CONCLUSIONSOral administration of metamizole for 4 days significantly altered the pharmacokinetics of both bupropion and its active metabolite, 4-hydroxybupropion, and significantly increased the CYP2B6-catalyzed bupropion hydroxylation in all of the subjects. Cautions should be taken when metamizole is co-administered with CYP2B6 substrate drugs.

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Section: Discussionmentioning

confidence: 74%

Rapid clinical induction of bupropion hydroxylation by metamizole in healthy Chinese men

Qin

Zhang

Liu

et al. 2012

Brit J Clinical Pharma

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“…Dry mouth is positively associated with mean bupropion metabolite concentrations, and is inversely related to patient weight (Johnston et al, 2001).…”

Section: (A) Antidepressantsmentioning

confidence: 99%

Adverse Drug Reactions in the Orofacial Region

Scully

Bagán

2004

Critical Reviews in Oral Biology & Medicine

215

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A wide spectrum of drugs can sometimes give rise to numerous adverse orofacial manifestations, particularly dry mouth, taste disturbances, oral mucosal ulceration, and/or gingival swelling. There are few relevant randomized double-blind controlled studies in this field, and therefore this paper reviews the data from case reports, small series, and non-peer-reviewed reports of adverse drug reactions affecting the orofacial region (available from a MEDLINE search to April, 2003). The more common and significant adverse orofacial consequences of drug therapy are discussed.

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“…Bupropion is an aminoketone used as an antidepressant and non-nicotine aid to smoking cessation (Johnston et al, 2001). It is extensively metabolized in vivo, and less than 10% of a bupropion dose is excreted unchanged (Schroeder, 1983).…”

Section: Introductionmentioning

confidence: 99%

In vivo evaluation of a transdermal codrug of 6-β-naltrexol linked to hydroxybupropion in hairless guinea pigs

Kiptoo

Paudel

Hammell

et al. 2008

European Journal of Pharmaceutical Sciences

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Abstract6-β-Naltrexol is the major active metabolite of naltrexone, NTX, a potent μ-opioid receptor antagonist used in the treatment of alcohol dependence and opioid abuse. Compared to naloxone, NTX has a longer duration of action largely attributed to 6-β-naltrexol. This study was carried out in order to determine percutaneous absorption of a transdermal codrug of naltrexol, 6-β-naltrexolhydroxybupropion codrug (CB-NTXOL-BUPOH), in hairless guinea pigs as well as to evaluate the safety of 6-β-naltrexol for development as a transdermal dosage form. This codrug may be useful in the simultaneous treatment of alcohol dependence and tobacco addiction. The carbonate codrug traversed the skin at a faster rate than 6-β-naltrexol. 6-β-naltrexol equivalent steady state plasma concentrations of 6.4 ng/ml were obtained after application of the codrug as compared to 1.2 ng/ml from 6-β-naltrexol base. The steady state plasma concentration of hydroxybupropion after codrug application was 6.9 ng/ml. Skin sensitization and irritation tested in the hairless guinea pigs using the Buehler method revealed that 6-β-naltrexol had no skin sensitizing potential. The method was validated with a known sensitizer, p-phenylenediamine, which induced sensitization in 90% of the animals. 6-β-Naltrexol caused only mild transient skin irritation after the initial application of the patch. During subsequent applications, erythema was slightly increased but no skin damage was observed. In conclusion, a transdermal codrug of 6-β-naltrexol could be a viable alternative treatment for alcohol and opiate abuse.

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Relationship between drug exposure and the efficacy and safety of bupropion sustained release for smoking cessation

Cited by 76 publications

References 10 publications

Rapid clinical induction of bupropion hydroxylation by metamizole in healthy Chinese men

Rapid clinical induction of bupropion hydroxylation by metamizole in healthy Chinese men

Adverse Drug Reactions in the Orofacial Region

In vivo evaluation of a transdermal codrug of 6-β-naltrexol linked to hydroxybupropion in hairless guinea pigs

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