Pharmacokinetics and Metabolism of Bisoprolol Enantiomers in Humans

Horikiri, Yuji; Suzuki, Takehiko; Mizobe, Masakazu

doi:10.1021/js970316d

Cited by 65 publications

(37 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3) Moreover, they suggested that CYP2D6 has a minor role but CYP3A4 plays a major part in the metabolism of bisoprolol, because the content of CYP2D6 in the human liver is much lower than that of CYP3A4. 3,20) The present findings that the non-renal clearance was not altered by the CYP2D6 and CYP2C19 genotypes may be consistent with the report of Horikiri et al 3,20) On the other hand, more than 30 single nucleotide polymorphisms have been identified in the CYP3A4 gene. 21) For the most common variant CYP3A4*1B, increased transcription was demonstrated in vitro, which may theoretically result in higher enzymatic activity in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…[3][4][5] In elderly patients, however, the age-associated decline in glomerular filtration and renal tubular secretion can affect the elimination of a drug dependent on the kidney for excretion. 6) In addition, hepatic drug metabolism may be diminished due to decreases in hepatic blood flow, liver mass, and levels of cytochrome P450 (CYP) drug-metabolizing enzymes.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetic Variability of Routinely Administered Bisoprolol in Middle-Aged and Elderly Japanese Patients

Taguchi

Nozawa

Igawa

et al. 2005

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Bisoprolol is a selective b 1 -blocker without intrinsic sympathomimetic activity, 1) and has been used widely in patients with cardiovascular diseases such as hypertension, angina pectoris, and cardiac arrhythmias in Japan. In healthy young subjects, 50% of the total dose of bisoprolol is metabolized in the liver, while 50% is excreted via the kidneys unchanged.2) The pharmacokinetics of bisoprolol shows less interindividual variability than that of other b-blockers because of a nearly complete absorption, small hepatic first-pass metabolism, and balanced renal excretion. [3][4][5] In elderly patients, however, the age-associated decline in glomerular filtration and renal tubular secretion can affect the elimination of a drug dependent on the kidney for excretion. 6) In addition, hepatic drug metabolism may be diminished due to decreases in hepatic blood flow, liver mass, and levels of cytochrome P450 (CYP) drug-metabolizing enzymes. 7,8) However, the pharmacokinetics of bisoprolol has not been clarified in routinely treated elderly Japanese patients.The present study was designed to evaluate the pharmacokinetic variability of routinely administered bisoprolol in middle-aged and elderly Japanese patients. A pharmacokinetic analysis was performed using a nonlinear mixed effects model (NONMEM). In addition, it is reported that drug metabolizing activity is often genetically polymorphic. 9) In this study, therefore, we also evaluated the effects of well-known genetic polymorphisms of CYP2D6 and CYP2C19 on the pharmacokinetic variability of bisoprolol. MATERIALS AND METHODS Subjects and Study ProtocolsThe subjects were 29 male and 11 female Japanese patients aged between 43 and 89 (meanϮS.D.: 63.5Ϯ10.1) years old, and mean body weight (ϮS.D.) was 63.8Ϯ10.7 kg. In this study, seven patients were characterized as having New York Heart Association (NYHA) class II congestive heart failure (CHF), but no patients had severe cardiac, hepatic, or renal failure. That is, mean (ϮS.D.) values of serum creatinine concentration, glutamic oxaloacetic transaminase activity, and glutamic pyruvic transaminase activity in the patients were 0.82Ϯ0.19 mg/dl (range: 0.50-1.30 mg/dl), 26Ϯ11 IU/l (range: 9-65 IU/l), and 29Ϯ26 IU/l (range: 4-160 IU/l), respectively. All patients had been routinely treated with an oral administration of bisoprolol hemifumarate (Maintate ® Tablets, Tanabe Pharmaceutical Co., Osaka, Japan) at doses of 2.5 or 5 mg/d, and the drug was administered once a day in all patients. No patients had received any potent inhibitor of CYP2D6 (e.g. amiodarone and quinidine) concomitantly. The total number of blood samples obtained at steady-state following repetitive administration was 94. That is, one or two blood samples for all 40 patients were obtained between 2.3 and 7.0 h after the administration. Additional blood samples just before administration were obtained in 36 patients. All patients (11 inpatients and 29 outpatients) gave written consent to participate in this study, which was approved by the ethics committee...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Pharmacokinetic Variability of Routinely Administered Bisoprolol in Middle-Aged and Elderly Japanese Patients

Taguchi

Nozawa

Igawa

et al. 2005

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…It is apparent that most of the commonly used β-blockers are either metabolized by CYP2D6 or eliminated by renal excretion 3,[12][13][14][15][16][17][18][19] ; thus, an awareness of which commonly used antidepressants significantly inhibit CYP2D6 10,11,[20][21][22][23][24][25] will warn clinicians about the risk of a potential drug interaction. Table 3 also lists antidepressants that are mild inhibitors of CYP2D6 10,23,25,26,[29][30][31] ; these are probably associated with lower risk of CYP2D6 drug interactions at usual clinical doses.…”

Section: Other Antidepressants and Other β-Blockersmentioning

confidence: 99%

Drug Interactions in the Treatment of Depression in Patients Receiving β-Blocker Drugs

Andrade¹

2013

J. Clin. Psychiatry

View full text Add to dashboard Cite

“…Il est sélectif de ces récepteurs cardiaques [4][5][6], limitant ainsi son tropisme vasculaire. Cette molécule a une action anti-ischémique et anti-arythmique.…”

Section: Rappels Pharmacologiquesunclassified

Intoxication volontaire au vérapamil et au bisoprolol : à propos d’un cas

et al. 2012

View full text Add to dashboard Cite

Résumé -Objectif : Le traitement de l'hypertension artérielle primaire fait appel à différents médicaments cardiotropes aux effets toxiques comparables. Notre travail relate, chez un patient traité pour hypertension, une double intoxication au vérapamil et au bisoprolol initialement étiquetée bisoprolol seul, lors d'un premier screening toxicologique large. Matériel et méthodes : Le diagnostic de cette intoxication a été obtenu par la répétition de recherches larges par une méthode CLHP/UV/BD. Résultats : La découverte de l'intoxication double au bisoprolol et au vérapamil a été permise grâce à deux screening toxicologiques successifs. Les concentrations toxiques de vérapamil sont apparues après la décroissance des concentrations toxiques de bisoprolol, expliquant la persistance, dans le temps, des symptômes cardiovasculaires. Cette intoxication a conduit le patient à séjourner en service de réanimation médicale pendant plusieurs jours. Les concentrations de vérapamil sont restées toxiques pendant 6 jours. Conclusion : Devant l'absence de modification des signes cliniques et la présence de forme galénique à libération prolongée, la répétition d'un screening toxicologique large plutôt qu'un dosage spécifique du toxique initialement suspecté, a permis le dépistage et le suivi d'une intoxication poly-médicamenteuse à molécules cardiotropes. Mots clés : Vérapamil, bisoprolol, intoxication, CLHPAbstract -Objective: Primary essential high blood pressure is treated by different cardiotropic drugs which have similar toxicological effects. Our study is about a verapamil and bisoprolol poisoning, which was at first labelled as bisoprolol only, after a comprehensive toxicological analysis. Materials and methods: This poisoning was diagnosed by repeated HPLC/UV/DAD screenings. Results: Two successive screenings showed both verapamil and bisoprolol poisoning. Verapamil toxic concentrations were revealed after the decrease in bisoprolol concentrations, explaining the persistence in time of cardiovascular symptoms. The patient stayed for several days in an intensive care unit. Verapamil concentrations remained at a toxic level for six days. Conclusion: Because of the presence of sustained-release forms and unchanged clinical signs, repeating a comprehensive toxicological screening, instead of monitoring the initially suspected drug, helped in the screening and the follow-up of this multiple cardiotopic drug poisoning.

show abstract

Pharmacokinetics and Metabolism of Bisoprolol Enantiomers in Humans

Cited by 65 publications

References 21 publications

Pharmacokinetic Variability of Routinely Administered Bisoprolol in Middle-Aged and Elderly Japanese Patients

Pharmacokinetic Variability of Routinely Administered Bisoprolol in Middle-Aged and Elderly Japanese Patients

Drug Interactions in the Treatment of Depression in Patients Receiving β-Blocker Drugs

Intoxication volontaire au vérapamil et au bisoprolol : à propos d’un cas

Contact Info

Product

Resources

About