Pharmacokinetics and Metabolism of Bisoprolol-14C in Three Animal Species and in Humans

Bühring, K U; Sailer, Hermann F.; Faro, Hans P.; Léopold, G; Pabst, J.; Garbe, Annette I.

doi:10.1097/00005344-198511001-00004

Cited by 34 publications

(24 citation statements)

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“…The absolute bioavailability (F) of S(-)-bisoprolol (89.8 ( 12.8%) was similar to that of R(+)-bisoprolol (93.3 ( 11.6%). Both values were close to the bioavailability of racemic bisoprolol reported in dogs (∼80%) 3 and in humans (90%) 4 .…”

Section: Resultssupporting

confidence: 86%

“…Bisoprolol is eliminated by two pathways, (i.e., hepatic metabolism and renal excretion [3][4][5], so the difference between CL t and CL r is the metabolic clearance (CL m ). These clearance values are summarized in Table 4.…”

Section: Resultsmentioning

confidence: 99%

“…1,2 The results of preclinical studies using several animals and clinical studies including healthy human subjects or patients, [3][4][5] indicate that bisoprolol has a high absolute bioavailability (90% of an oral dose) due to its nearly complete enteral absorption (>90%) and a very small firstpass effect (<10%). A long elimination half-life (10-12 h) allows this drug to be used on a once-a-day dosage regimen.…”

Section: Introductionmentioning

confidence: 99%

“…Also, we elucidated the pharmacokinetic properties of bisoprolol enantiomers in dogs, which are known to exhibit similar pharmacokinetic profiles of racemic bisoprolol, such as bioavailability, metabolic pathways, and urinary excretion, as in humans. 3 …”

Section: Introductionmentioning

confidence: 99%

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Stereoselective Pharmacokinetics of Bisoprolol After Intravenous and Oral Administration in Beagle Dogs

Horikiri¹,

Suzuki²,

Mizobe³

1997

Journal of Pharmaceutical Sciences

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The stereoselective pharmacokinetics of bisoprolol, a highly beta 1-selective adrenoceptor blocking agent, was studied in dogs. After intravenous and oral administration of the racemate, there was a difference in the plasma concentration between S(-)- and R(+)-bisoprolol. The area under the curve (AUC) of concentration versus time of S(-)-bisoprolol was approximately 1.5 times higher than that of R(+)-bisoprolol and the elimination half-life of S(-)-bisoprolol was approximately 1.4 times longer than that of R(+)-bisoprolol. However, no differences were observed in the volume of distribution, absolute bioavailability, and renal clearance between the two enantiomers. The plasma protein binding of S(-)-bisoprolol was also the same as that of the R(-)-isomer. No chiral inversion or enantiomer-enantiomer interaction was observed, when enantiomers were solely administered via the intravenous route. The comparison of the oxidative metabolic rate of two enantiomers using dog liver microsomes demonstrated that the metabolite was more slowly formed from S(-)- than from R(+)-bisoprolol. Consequently, we concluded that the stereoselective difference in the metabolic clearance between S(-)- and R(+)-bisoprolol caused the difference in the disposition of bisoprolol enantiomers.

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Section: Resultssupporting

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Stereoselective Pharmacokinetics of Bisoprolol After Intravenous and Oral Administration in Beagle Dogs

Horikiri¹,

Suzuki²,

Mizobe³

1997

Journal of Pharmaceutical Sciences

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“…[6][7][8][16][17][18][19][20][21] For K d , the values reported by Baker, who examined the three agents simultaneously, were used.…”

Section: Collection Of Pharmacokinetic and Pharmacodynamic Parametersmentioning

confidence: 99%

Analysis of Clinical Efficacy and Adverse Effects of β-Blocking Agents Used Clinically for Chronic Heart Failure

Takayanagi

Fujito

Kimura

et al. 2017

Biological & Pharmaceutical Bulletin

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Clinical efficacy and adverse effects of the β-blocking agents, carvedilol, bisoprolol, and metoprolol were analyzed theoretically, and then compared quantitatively, for the purpose of determining their proper use for chronic heart failure. Initially, we evaluated occupancy binding to the β 1 and β 2 receptors (Фss β 1 and Фss β 2 ) by these drugs. Thereafter, we examined the relationship between Фss β 1 values and left ventricular ejection fraction (LVEF) increase rate to determine efficacy. The result showed that the efficacy with carvedilol could be attained with a lower Фss β 1 value than the others. Therefore, we constructed a model under the assumption that β-blocking agents exert both indirect action of LVEF increase through the β 1 receptor and direct action on ryanodine receptor 2. Using the model, it was suggested that these drugs have no differences in regard to the efficacy, while it was clarified theoretically that only carvedilol produces an effect that directly involves ryanodine receptor 2 at clinical doses. We also investigated decreases in heart rate and forced expiratory volume in 1 s as adverse effects of β-blocking agents using a ternary complex model. It was indicated that carvedilol is less likely to induce a heart rate decrease. Meanwhile, it was also suggested that the risk of an asthmatic attack was higher for carvedilol at clinical doses. Our results are considered useful for selection of a proper β-blocking agent and its administration at a reasonable dose for successful heart failure therapy.

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The use of electron impact and positive chemical ionization mass spectrometry in the screening of beta blockers and their metabolites in human urine

Leloux

Maes

1990

Biol. Mass Spectrom.

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The use of several mass spectrometry technologies including electron impact (EI) and positive chemical ionization (CI) in both full-scan and multiple ion detection (MID) analysis for the urine analysis of several beta blockers and metabolites has been investigated. These drugs were extracted using an alkaline solid-phase extraction procedure and identified as their respective trimethylsilyl-trifluoroacetyl (TMS-TFA) derivatives on capillary gas chromatography/mass spectrometry. Isobutane proved to be the preferred reagent gas for the positive CI mass spectrometry of TMS-TFA derivatives of beta blockers, in comparison with others, such as methanol, ammonia and methane, since mass spectra with little fragmentation and abundant ions at high mass were obtained. By combining EI mass spectrometry and isobutane positive CI mass spectrometry using the ion trap detector, the identities of the main co-extracted metabolites were confirmed. Absolute detection limits were 0.15 ng for full-scan analysis (EI as well as positive CI mass spectrometry) and 0.08 ng for MID analysis (EI as well as CI mass spectrometry). The detection times of beta blockers in human urine were at least two- to three-fold the elimination half-life of these drugs. The analytical potential of the above mass spectrometric techniques has been discussed.

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Pharmacokinetics and Metabolism of Bisoprolol-14C in Three Animal Species and in Humans

Cited by 34 publications

References 0 publications

Stereoselective Pharmacokinetics of Bisoprolol After Intravenous and Oral Administration in Beagle Dogs

Stereoselective Pharmacokinetics of Bisoprolol After Intravenous and Oral Administration in Beagle Dogs

Analysis of Clinical Efficacy and Adverse Effects of β-Blocking Agents Used Clinically for Chronic Heart Failure

The use of electron impact and positive chemical ionization mass spectrometry in the screening of beta blockers and their metabolites in human urine

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