Pharmacokinetics and Metabolism of Diltiazem in Man

Rovei,; Goméni, Roberto; Mitchard, M.; Larribaud, J; Blatrix, C; Jj, Thebault; Pl, Morselli

doi:10.1016/b978-0-08-023768-8.51690-x

Cited by 40 publications

(23 citation statements)

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“…The absolute bioavailability of the tablets ranges between 30 and 42 % largely due to presystemic hepatic metabolism [3,4]. After absorption, diltiazem undergoes extensive hepatic metabolism through three major metabolic pathways, N-demethylation, O-deacetylation, and O-demethylation [2][3][4][5]. Diltiazem undergoes hydrolysis to desacetyl diltiazem in acidic solutions and is most stable at pH 5.…”

Section: Introductionmentioning

confidence: 99%

Voltammetric sensor based on Co3O4/SnO2 nanopowders for determination of diltiazem in tablets and biological fluids

et al. 2016

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In this work, an anodic stripping voltammetry for nanomolar determination of diltiazem with a chemically modified carbon paste electrode (CMCPE) containing Co 3 O 4 / SnO 2 nanopowders was studied. The accumulation potential and time were selected at, -0.2 V and 190 s, respectively. The electroanalytical performance of the CMCPE was evaluated regarding the carbon paste composition, the solution pH, the time and potential accumulation, and the potential interferences. The novel electrode showed linear response to diltiazem concentration range of 50-650 nM with a lowest detection limit value of 15 nM. The precisions for six consecutive determinations of 350 and 550 nM diltiazem were 3.2 and 2.5 %, respectively. It was demonstrated that the proposed method was free from most interference. Finally, the method was effectively applied to the determination of diltiazem in pharmaceutical tablets and biological samples.

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Section: Introductionmentioning

confidence: 99%

Voltammetric sensor based on Co3O4/SnO2 nanopowders for determination of diltiazem in tablets and biological fluids

et al. 2016

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“…The apparent terminal elimination halflife of 15.2 h in our patient is similar to half-lives observed by others following overdose of the standard formulation (range 9-16 h), [5,24,25] but longer than the 4-7 h reported in therapeutic dosing. [1,15,[26][27][28] This may relate to saturation of hepatic clearance [29], however it is not possible to exclude ongoing absorption at this time, hence the term 'apparent terminal elimination' [8].…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately its identity and concentration could not be confirmed because of difficulty in obtaining analytical grade MA. It is a major metabolite with approximately 20% of the potency of diltiazem [15] so its clearance by HP was considered.…”

Section: Analysesmentioning

confidence: 99%

Lessons learnt in the pharmacokinetic analysis of the effect of haemoperfusion for acute overdose with sustained‐release diltiazem

Roberts

Mason

et al. 2008

Anaesthesia

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SummaryThe effect of charcoal haemoperfusion on the pharmacokinetics of diltiazem is described in a patient with severe clinical toxicity following acute overdose. The patient presented within 3 h following acute ingestion of multiple medications including sustained-release diltiazem. Routine resuscitation and supportive care were administered, but hypotension did not resolve despite intravenous fluids and infusions of calcium, adrenaline, noradrenaline and vasopressin. Multipledoses of activated charcoal, haemodialysis and charcoal haemoperfusion were prescribed to expedite the elimination of diltiazem. The maximum diltiazem concentration (577 lg.l )1 ) was recorded 7 h post ingestion which was followed by an erratic and prolonged elimination phase.The maximum clearance of diltiazem due to haemoperfusion was calculated to be 19.4 and 15.1 ml.min )1 at different times, equating to removal of approximately 1.5 mg diltiazem during 4 h of haemoperfusion. Haemoperfusion did not appear to remove sufficient diltiazem to recommend its routine use in the treatment of patients with acute diltiazem overdose. Severe cardiovascular depression and death is reported from self-poisoning with diltiazem. In overdose these effects manifest as bradycardia and hypotension which relates more to decreased systemic vascular resistance than cardiac contractility [1]. Standard and sustained-release formulations of diltiazem differ in their pharmacokinetic profile. Acute poisoning with the standard formulation usually leads to a rapid onset of toxicity which largely resolves within 12 h. This differs from the more frequently used sustainedrelease formulation where toxicity is delayed in onset and prolonged [1,2]. For example, in two recent cases only mild hypotension preceded the development of a cardiac arrest more than 13 and 18 h post ingestion [3,4]. The variable time-course of toxicity relates to unpredictable changes in the concentration of diltiazem. This may reflect erratic absorption from an aggregate of sustainedrelease tablets [2], or dose-related factors such as ileus [5][6][7] or changes in clearance due to enzyme saturation or hepatic hypoperfusion with marked hypotension [1,8].The initial management of acute diltiazem poisoning includes gastrointestinal decontamination and the administration of intravenous fluids and calcium. Unfortunately, many cases are refractory to these first-line treatments, requiring other interventions, including atropine, glucagon, vasopressors, temporary pacing, balloon pump,

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“…Only desacetyldiltiazem is pharmacologically active, but its activity is only about 40-50 per cent that of diltiazem. 16 In human adults the elimination half time of diltiazem is 4.5 to 4.9 hours after intravenous infusion of 20 mg over ten minutes, an oral dose of 60 to 90 mg, or repeated oral administration of 60 or 90 mg every six hours for four days. 17 After repeated administration, accumulation of both diltiazem and its metabolite, deacetyldiltiazem occur.…”

Section: Comparison Of Diltiazem With Other Calcium Antagonists and Amentioning

confidence: 99%

Diltiazem

Britt

1985

Can. Anaesth. Soc. J.

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Pharmacokinetics and Metabolism of Diltiazem in Man

Cited by 40 publications

References 0 publications

Voltammetric sensor based on Co3O4/SnO2 nanopowders for determination of diltiazem in tablets and biological fluids

Voltammetric sensor based on Co3O4/SnO2 nanopowders for determination of diltiazem in tablets and biological fluids

Lessons learnt in the pharmacokinetic analysis of the effect of haemoperfusion for acute overdose with sustained‐release diltiazem

Diltiazem

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