The single dose pharmacokinetics of bisoprolol (10 mg) in renal insufficiency: the clinical significance of balanced clearance

Payton, C. D.; Fox, Jonathan G.; Pauleau, N.; Boulton‐Jones, J. M.; Ioannides, Costas; Johnston, Atholl; Thomas, Paul J.

doi:10.1093/eurheartj/8.suppl_m.15

Cited by 23 publications

(16 citation statements)

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“…This finding contrasts with those for many of the other quinolones that are eliminated almost exclusively by either hepatic metabolism (grepafloxacin) (8) or urinary excretion (levofloxacin) (15). Results from work with other agents that are eliminated by multiple pathways (such as bisoprolol by the liver and kidney) (18) suggest that the overall elimination of garenoxacin may not be substantially altered in patients with either renal or hepatic insufficiency and could thus potentially simplify dosing in these patient groups.…”

Section: Discussionmentioning

confidence: 90%

Multiple-Dose Safety and Pharmacokinetics of Oral Garenoxacin in Healthy Subjects

Gajjar

Bello

et al. 2003

Antimicrob Agents Chemother

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Garenoxacin (T-3811ME, BMS-284756) is a novel des-F(6) quinolone that has been shown to be effective in vitro against a wide range of clinically important pathogens, including gram-positive and gram-negative aerobes and anaerobes. This study was conducted to evaluate the safety and tolerability of multiple oral doses (100 to 1,200 mg/day) of garenoxacin in healthy subjects and to determine its multiple-dose pharmacokinetics. Forty healthy male and female subjects (18 to 45 years of age) were enrolled in this randomized, double-blind, placebo-controlled, sequential, multiple-and ascending-dose study. Each subject received a once-daily oral dose of garenoxacin (100, 200, 400, 800, or 1,200 mg) or a placebo for 14 days. Blood and urine samples were collected for measurements of garenoxacin by validated liquid chromatography with dual mass spectrometry, and plasma garenoxacin concentration-time data were analyzed by noncompartmental methods. The effects of garenoxacin on Helicobacter pylori, psychometric test performance, and electrocardiograms were assessed, as was drug safety. Over the 14 days of dosing, geometric mean peak concentrations of garenoxacin in plasma (C max ) at the 100-and 1,200-mg doses were within the ranges of 1.2 to 1.6 and 16.3 to 24 g/ml, respectively. The corresponding values for the geometric mean area under the concentration-time curve over the dosing interval (AUC ) for garenoxacin in plasma at the 100-and 1,200-mg doses were within the ranges of 11.5 to 15.7 and 180 to 307 g ⅐ h/ml, respectively. Increases in systemic exposure to garenoxacin in terms of AUC and C max were approximately dose proportional over the 100-to 400-mg dose range but demonstrated increases that were somewhat greater than the dose increments at the 800-and 1,200-mg doses. Median values for the time to achieve C max were in the range of 1.13 to 2.50 h for all doses. The mean elimination half-life for garenoxacin in plasma appeared to be independent of dose and ranged from 13.3 to 17.8 h (day 14). Approximately 30 to 50% of an administered garenoxacin dose was excreted unchanged in the urine. At doses of 100 to 400 mg, steady-state concentrations of garenoxacin in plasma appeared to be attained by the fourth dose. Multiple oral doses of garenoxacin were well tolerated and did not demonstrate clinically significant effects on QT c or psychometric test results. Garenoxacin administered alone for 14 days at doses of >400 mg demonstrated activity against H. pylori. These results suggest that multiple once-daily oral doses of garenoxacin of up to 1,200 mg are safe and well tolerated and that the pharmacokinetics of garenoxacin support once-daily administration.

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Section: Discussionmentioning

confidence: 90%

Multiple-Dose Safety and Pharmacokinetics of Oral Garenoxacin in Healthy Subjects

Gajjar

Bello

et al. 2003

Antimicrob Agents Chemother

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“…It is removed from the body by renal excretion and hepatic metabolism, and with normal organ function, the two clearance pathways are equally important [12,13]. Bisoprolol is equally hydrophilic and lipophilic, only 30 % is bound to plasma proteins, and its volume of distribution >200 L suggests binding to tissue proteins [14].…”

Section: Introductionmentioning

confidence: 99%

Bisoprolol pharmacokinetics and body composition in patients with chronic heart failure: a longitudinal study

Trobec

Grabnar

Kos

et al. 2016

Eur J Clin Pharmacol

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In patients with chronic heart failure, bisoprolol clearance was associated with estimated renal function; thus, in moderately and severely decreased renal function, patients may need to have their dose adjusted. Patients with low body weight or low SMI have greater fluctuations and higher maximal plasma concentrations of bisoprolol because of the lower volume of distribution. Longitudinal changes of bisoprolol pharmacokinetics were not associated with changes in body composition.

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“…Acebutolol, atenolol, and metoprolol have high dialyzablility, 4-9 whereas bisoprolol and propranolol have low dialyzablility. [10][11][12][13][14] This characteristic could theoretically affect patient outcomes by lowering the average plasma concentration achieved in patients receiving high-dialyzability agents. We conducted this study to test the hypothesis that among patients receiving long-term hemodialysis, initiation of high-dialyzability b-blockers was associated with higher risks of death and cardiovascular events compared with low-dialyzability b-blockers.…”

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confidence: 99%

β-Blocker Dialyzability and Mortality in Older Patients Receiving Hemodialysis

Weir

Dixon

Fleet

et al. 2015

Journal of the American Society of Nephrology

102

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Some b-blockers are efficiently removed from the circulation by hemodialysis ("high dialyzability") whereas others are not ("low dialyzability"). This characteristic may influence the effectiveness of the b-blockers among patients receiving long-term hemodialysis. To determine whether new use of a highdialyzability b-blocker compared with a low-dialyzability b-blocker associates with a higher rate of mortality in patients older than age 66 years receiving long-term hemodialysis, we conducted a propensity-matched population-based retrospective cohort study using the linked healthcare databases of Ontario, Canada. The high-dialyzability group (n=3294) included patients initiating atenolol, acebutolol, or metoprolol. The low-dialyzability group (n=3294) included patients initiating bisoprolol or propranolol. Initiation of a highversus low-dialyzability b-blocker was associated with a higher risk of death in the following 180 days (relative risk, 1.4; 95% confidence interval, 1.1 to 1.8; P,0.01). Supporting this finding, we repeated the primary analysis in a cohort of patients not receiving hemodialysis and found no significant association between dialyzability and the risk of death (relative risk, 1.0; 95% confidence interval, 0.9 to 1.3; P=0.71). b-Blocker exposure was not randomly allocated in this study, so a causal relationship between dialyzability and mortality cannot be determined. However, our findings should raise awareness of this potentially important drug characteristic and prompt further study.

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The single dose pharmacokinetics of bisoprolol (10 mg) in renal insufficiency: the clinical significance of balanced clearance

Cited by 23 publications

References 0 publications

Multiple-Dose Safety and Pharmacokinetics of Oral Garenoxacin in Healthy Subjects

Multiple-Dose Safety and Pharmacokinetics of Oral Garenoxacin in Healthy Subjects

Bisoprolol pharmacokinetics and body composition in patients with chronic heart failure: a longitudinal study

β-Blocker Dialyzability and Mortality in Older Patients Receiving Hemodialysis

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