Pharmacokinetic and pharmacodynamic modelling of atenolol in rabbits maintained on continuous peritoneal dialysis

Celardo, Antonio; Traina, G. L.; Arboix, M.; Puigdemont, Anna; Bonati, Maurizio

doi:10.1007/bf03189860

Cited by 3 publications

(9 citation statements)

References 22 publications

(17 reference statements)

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“…As expected, anuria was associated with a ninefold decrease of atenolol elimination and a prolongation of drug effect during anuria [43]. Nevertheless, by using an effect compartmental model, the authors did not found differences in main PK/PD parameters, E max and EC 50 , of atenolol chronotropic effect comparing rabbits before and during renal failure [43].…”

Section: Preclinical Pk/pd Studies With β-Blockersmentioning

confidence: 71%

“…Nevertheless, by using an effect compartmental model, the authors did not found differences in main PK/PD parameters, E max and EC 50 , of atenolol chronotropic effect comparing rabbits before and during renal failure [43]. These results suggest that reduction of kidney function alters atenolol PK properties without affecting their PD profile [43]. In rabbits with experimental liver failure, Bortolloti et al [44] have evaluated the impact of liver injury on PK/PD properties of metoprolol, a lipophilic second-generation β-blocker that undergoes extensive biotransformation.…”

Section: Preclinical Pk/pd Studies With β-Blockersmentioning

confidence: 90%

“…For instance, as atenolol is a second-generation β-blocker with predominantly renal elimination, Celardo et al [43] have assessed the influence of renal failure on the PK and PD profiles of atenolol in adult male rabbits on continuous peritoneal dialysis. As expected, anuria was associated with a ninefold decrease of atenolol elimination and a prolongation of drug effect during anuria [43].…”

Section: Preclinical Pk/pd Studies With β-Blockersmentioning

confidence: 99%

“…Influence of renal function on PK/PD properties of atenolol Impact of live injury on PK/PD properties of metoprolol Influence of protein binding on chronotropic effect of S-propranolol Relevance of sympathetic overactivity in the maintenance of hypertension Contribution of sympatholytic activity of carvedilol on antihypertensive response Characterization of sustained-release formulations of atenolol [43].…”

Section: Preclinical Pk/pd Modelingmentioning

confidence: 99%

See 3 more Smart Citations

PK/PD Modeling of β-Blockers in Cardiovascular Disease: An Update

Höcht

Bertera

Mauro

et al. 2016

Int. J. Pharmacokinet.

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Review β-blockers play a central role in the treatment of the various main cardiovascular diseases, including hypertension, coronary artery disease and systolic heart failure. As a therapeutic class, β-blockers form a heterogeneous family that differs in their pharmacokinetic (PK) and pharmacodynamic (PD) properties, highlighting the relevance of the extensive evaluation of PK/PD properties of these agents in order to optimize the outcomes of the treatment of cardiovascular diseases. Preclinical and clinical studies using PK/PD models have been able to identify different factors associated with cardiovascular response of β-blockers, including age, pharmaceutical formulation and genetic polymorphism, among others. PK/PD modeling of β-blockers can also be attractive for the early detection of poor responders and the optimization of dose regimen in their different indications.

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Section: Preclinical Pk/pd Studies With β-Blockersmentioning

confidence: 71%

Section: Preclinical Pk/pd Studies With β-Blockersmentioning

confidence: 90%

Section: Preclinical Pk/pd Studies With β-Blockersmentioning

confidence: 99%

Section: Preclinical Pk/pd Modelingmentioning

confidence: 99%

See 2 more Smart Citations

PK/PD Modeling of β-Blockers in Cardiovascular Disease: An Update

Höcht

Bertera

Mauro

et al. 2016

Int. J. Pharmacokinet.

View full text Add to dashboard Cite

show abstract

“…By using an effect-compartment model, Celardo et al [72] evaluated the influence of renal failure on the PK and PD profiles of atenolol in adult male rabbits on continuous peritoneal dialysis. The authors reported a ninefold decrease of atenolol elimination and an increase in duration of drug effect during anuria [72].…”

Section: Preclinical Pk/pd Models Of B-blockersmentioning

confidence: 99%

Models for evaluating the pharmacokinetics and pharmacodynamics for β-blockers

Höcht

Bertera

Mauro

et al. 2014

Expert Opinion on Drug Metabolism & Toxicology

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PK models and PK/PD modeling have clearly contributed to characterization of the PK and PD properties of β-blockers. Differences in cardiovascular actions between classical β-blockers and vasodilatory β-blockers need to be further studied in order to confirm the clinical benefits of the new-generation of β-blockers. PK/PD modeling may contribute to clarify the importance of heterogeneity of PK and PD properties of β-blockers potentially improving the selection of the adequate agent and dose regimen in the treatment of cardiovascular diseases.

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Extracorporeal treatment for poisoning to beta-adrenergic antagonists: systematic review and recommendations from the EXTRIP workgroup

et al. 2021

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Background β-adrenergic antagonists (BAAs) are used to treat cardiovascular disease such as ischemic heart disease, congestive heart failure, dysrhythmias, and hypertension. Poisoning from BAAs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in BAAs poisoning. Methods We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods. Results A total of 76 studies (4 in vitro and 2 animal experiments, 1 pharmacokinetic simulation study, 37 pharmacokinetic studies on patients with end-stage kidney disease, and 32 case reports or case series) met inclusion criteria. Toxicokinetic or pharmacokinetic data were available on 334 patients (including 73 for atenolol, 54 for propranolol, and 17 for sotalol). For intermittent hemodialysis, atenolol, nadolol, practolol, and sotalol were assessed as dialyzable; acebutolol, bisoprolol, and metipranolol were assessed as moderately dialyzable; metoprolol and talinolol were considered slightly dialyzable; and betaxolol, carvedilol, labetalol, mepindolol, propranolol, and timolol were considered not dialyzable. Data were available for clinical analysis on 37 BAA poisoned patients (including 9 patients for atenolol, 9 for propranolol, and 9 for sotalol), and no reliable comparison between the ECTR cohort and historical controls treated with standard care alone could be performed. The EXTRIP workgroup recommends against using ECTR for patients severely poisoned with propranolol (strong recommendation, very low quality evidence). The workgroup offered no recommendation for ECTR in patients severely poisoned with atenolol or sotalol because of apparent balance of risks and benefits, except for impaired kidney function in which ECTR is suggested (weak recommendation, very low quality of evidence). Indications for ECTR in patients with impaired kidney function include refractory bradycardia and hypotension for atenolol or sotalol poisoning, and recurrent torsade de pointes for sotalol. Although other BAAs were considered dialyzable, clinical data were too limited to develop recommendations. Conclusions BAAs have different properties affecting their removal by ECTR. The EXTRIP workgroup assessed propranolol as non-dialyzable. Atenolol and sotalol were assessed as dialyzable in patients with kidney impairment, and the workgroup suggests ECTR in patients severely poisoned with these drugs when aforementioned indications are present.

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Pharmacokinetic and pharmacodynamic modelling of atenolol in rabbits maintained on continuous peritoneal dialysis

Cited by 3 publications

References 22 publications

PK/PD Modeling of β-Blockers in Cardiovascular Disease: An Update

PK/PD Modeling of β-Blockers in Cardiovascular Disease: An Update

Models for evaluating the pharmacokinetics and pharmacodynamics for β-blockers

Extracorporeal treatment for poisoning to beta-adrenergic antagonists: systematic review and recommendations from the EXTRIP workgroup

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