Pharmacokinetics of conventional and slow‐release verapamil.

Folláth, Ferenc; Ha, Huy Riêm; Schütz, E; Fr, Bühler

doi:10.1111/j.1365-2125.1986.tb02864.x

Cited by 25 publications

(13 citation statements)

References 15 publications

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“…Verapamil is metabolized by CYP3A, which is found to have a minor diurnal pattern, with CYP3A activity lowest around 3 AM and highest in the afternoon. The plasma concentration of verapamil after administration of immediate release verapamil varies greatly and is more stable after administration of sustained release tablets (Table ). Plasma concentration and bioavailability of verapamil depend on multiple factors.…”

Section: Side Effects and Safetymentioning

confidence: 99%

“…Plasma concentration and bioavailability of verapamil depend on multiple factors. The bioavailability of sustained release tablets is around 90% compared to immediate release but with a large variability . With immediate release tablets the bioavailability is increased by 5%‐points in women compared to men .…”

Section: Side Effects and Safetymentioning

confidence: 99%

“…With immediate release tablets the bioavailability is increased by 5%‐points in women compared to men . Normally, immediate release verapamil peaks in plasma concentration after 1‐2 hours, but the level is dependent on time of dosage. The highest plasma concentration is achieved in the morning compared to the afternoon, evening, or nighttime (immediate release), however, this is a single‐dose study and might not be relevant in steady state.…”

Section: Side Effects and Safetymentioning

confidence: 99%

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Verapamil and Cluster Headache: Still a Mystery. A Narrative Review of Efficacy, Mechanisms and Perspectives

et al. 2019

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Objective A evaluation of the effect of verapamil and other calcium channel blockers in cluster headache (CH) treatment and an investigation of possible effect mechanisms. Background Verapamil has been used in the prevention of CH for almost 3 decades, however, the mode of action and therapeutic target is still unknown. Methods A Pubmed search was conducted: “Verapamil”[Mesh] and “Cluster Headache”[Mesh]. We identified 5 relevant studies for CH. Publications were included if they made a substantial contribution within 3 prespecified areas: Efficacy (randomized controlled‐trials or open labels studies), safety, and mechanism of effect. Results Clinical effect: Clinical preventive treatment of CH with verapamil is based on 2 randomized controlled studies and 3 open‐label studies. In total, 183 CH patients participated. Verapamil 360 mg/day was used in both controlled studies. Half of the chronic patients experienced benefit from verapamil treatment and the attack burden of episodic patients was, on average, reduced by 1 attack/day. Open‐label studies support a dose‐dependent level of efficacy. Mechanism of effect: Human and animal studies indicate that verapamil may exert its effect by modulating circadian rhythms, perhaps in central pacemakers, and/or by affecting release of calcitonin gene‐related peptide. Conclusion Verapamil appears to be an effective prophylactic drug in the treatment of CH and despite the scarcity of controlled trials, it is still the drug of choice. A chronotherapeutic approach might increase the effect. More basic and pharmacokinetic research is needed before the mechanism can be fully understood.

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Section: Side Effects and Safetymentioning

confidence: 99%

Section: Side Effects and Safetymentioning

confidence: 99%

Section: Side Effects and Safetymentioning

confidence: 99%

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Verapamil and Cluster Headache: Still a Mystery. A Narrative Review of Efficacy, Mechanisms and Perspectives

et al. 2019

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“…The immediate release form reaches peak plasma concentrations within two hours but sustained release preparations do not reach maximal serum concentrations until 3 Á/9 hours post ingestion. 9 Thus, symptomatic presentation may be delayed with sustained release intoxication. Verapamil is hepatically metabolized by extensive firstpass metabolism by N-methylation to norverapamil, an active metabolite.…”

Section: Discussionmentioning

confidence: 99%

Successful resuscitation of a verapamil intoxicated child with a dextrose-insulin infusion

MT¹,

Stremski²,

Scanlon³

2003

Clinical Intensive Care

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Objective: To report the use of dextrose-insulin infusion in the successful resuscitation of an adolescent following an overdose of sustained-release verapamil that was refractory to traditional medical management. Case summary: A 13-year-old female with depression and post-traumatic stress disorder ingested 25 Á/30 120-mg tablets (120 Á/140 mg/kg) of sustained-release verapamil in a suicide attempt. Gastric lavage was performed, and activated charcoal and sorbitol were given for gastric decontamination. She developed atrial-ventricular (A-V) dissociation, bradycardia, hypotension and somnolence. Initial interventions included endotracheal intubation for airway protection, fluid resuscitation, highdose intravenous calcium chloride, and glucagon. Hypotension and A-V block continued despite the addition of dopamine, epinephrine, and norepinephrine infusions. Normal sinus rhythm and hemodynamic stability occurred only after an infusion of regular insulin (0.1 U/kg/hr) and dextrose (0.5 g/kg/hr) was started. She was weaned from vasopressor infusions over the next 48 hours and she was successfully extubated. Follow-up cardiac evaluation was normal. Conclusion: In this report, insulin euglycemia adjunctive therapy was used for the successful resuscitation of a severe verapamil intoxication that was refractory to standard therapies.

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“…Une recherche sanguine de bisoprolol est donc demandée en urgence au laboratoire de Toxicologie. Cette recherche, réalisée par criblage en chromatographie liquide couplée à la spectrométrie de masse en tandem, ne met pas en évidence de bisoprolol mais retrouve du vérapamil en concentration toxique (1,7 mg/L ; valeurs thérapeutiques : 0,02-0,25 mg/L [7,8]). …”

Section: Description Du Casunclassified

Découverte fortuite d’une intoxication aiguë par vérapamil forme à libération prolongée : intérêt du criblage toxicologique

et al. 2012

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Résumé -Objectifs : Un patient de 29 ans a été admis en soins intensifs pour hypotension résistante et anomalies du rythme cardiaque. Le service clinique suspectant une intoxication par bisoprolol, un criblage toxicologique par chromatographie liquide couplée à la spectrométrie de masse en tandem (LC-MS/MS) a été réalisé. Ce criblage n'a pas retrouvé de bisoprolol mais a mis en évidence une intoxication par vérapamil. Afin de confirmer l'intoxication, des dosages sanguins du vérapamil et de ses principaux métabolites ont été effectués quotidiennement. Méthodes : La recherche et les dosages ont été réalisés par LC-MS/MS. Les métabolites ont été préalablement identifiés après incubation du vérapamil avec des microsomes hépatiques de souris. Résultats : Sept métabolites ont été identifiés après incubation avec les microsomes hépatiques de souris. Cinq d'entre eux ont été retrouvés dans le sérum du patient. L'évolution des taux sanguins en véra-pamil a montré une croissance le 1 er jour (1,0 mg/L à J1, 1,7 mg/L à J2 ; valeurs thérapeutiques : 0,02 à 0,25 mg/L), un plateau pendant 3 jours puis une décroissance. Les cinétiques des principaux métabolites du vérapamil (norvérapamil et N-desalkylvérapamil) étaient comparables à celle de la molécule mère. Conclusion : Le criblage toxicologique a permis de diagnostiquer l'intoxication par vérapamil dans un contexte clinique complexe. La stagnation des taux sanguins pendant 3 jours était vraisemblablement due à une intoxication avec une forme à libération prolongée du vérapamil. Mots clés : Vérapamil, intoxication aiguë, criblage toxicologique, LC-MS/MSAbstract -Objectives: A 29-year old man was admitted in intensive care unit for resistant hypotension and cardiac rhythm disturbances. Since a bisoprolol overdose was suspected, a toxicological screening was carried out on serum. This screening didn't show bisoprolol but revealed verapamil intoxication. To confirm the diagnosis, verapamil and its main metabolites were assayed on 6 serum samples taken over the period of hospitalization. Methods: Verapamil and metabolites were identified by LC-MS/MS. Metabolites have been previously recognized after mouse liver microsomal incubation and added to the data library. Results: Seven verapamil metabolites were identified after mouse liver microsomal incubation. Five of them were found in serum samples. Kinetics of verapamil and its main metabolites (norverapamil and N-desalkylverapamil) in serum samples revealed 3 stages: increase during the 1st day, stability during 3 days and decrease on 5th and 6th days. Conclusion: The present case demonstrates the importance of toxicological screening in the diagnosis of drugs overdose. The stagnation of serum levels during 3 days could be explained by intoxication with a sustained-release formulation of verapamil.

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Pharmacokinetics of conventional and slow‐release verapamil.

Cited by 25 publications

References 15 publications

Verapamil and Cluster Headache: Still a Mystery. A Narrative Review of Efficacy, Mechanisms and Perspectives

Verapamil and Cluster Headache: Still a Mystery. A Narrative Review of Efficacy, Mechanisms and Perspectives

Successful resuscitation of a verapamil intoxicated child with a dextrose-insulin infusion

Découverte fortuite d’une intoxication aiguë par vérapamil forme à libération prolongée : intérêt du criblage toxicologique

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