Serum Concentration and Antihypertensive Effect of Slow-Release Verapamil

Schütz, E; Ha, Huy Riêm; Bühler, Fritz R.; Folláth, Ferenc

doi:10.1097/00005344-198200433-00017

Cited by 53 publications

(7 citation statements)

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“…Whereas in the study by Storstein et al (1981), plasma verapamil concentrations were significantly correlated with the blood pressure lowering effect, no such correlation was observed in the study by Schuetz et al (1982).…”

Section: Verapamilmentioning

confidence: 70%

Clinical Pharmacokinetics of Verapamil, Nifedipine and Diltiazem

Echizen

Eichelbaum

1986

Clinical Pharmacokinetics

180

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The calcium antagonists diltiazem, nifedipine and verapamil are widely used in the treatment of coronary heart disease, arterial hypertension, certain supraventricular tachyarrhythmias and obstructive hypertrophic cardiomyopathy. During recent years their pharmacokinetic properties and metabolism have been studied in more detail. Although these 3 calcium antagonists exhibit great diversity in chemical structure, they exhibit common pharmacokinetic properties. These drugs are extensively metabolised and only traces of unchanged drugs are eliminated in urine. Their systemic plasma clearances are high and dependent on liver blood flow. Therefore, their bioavailabilities (diltiazem 40 to 50%; nifedipine 40 to 50%; verapamil 10 to 30%) are low despite almost complete absorption following oral administration. During long term treatment, oral clearance decreases and bioavailability increases due to saturation of hepatic first-pass metabolism. Pronounced intra- and inter-individual variations in clearance and bioavailability are observed. In patients with liver cirrhosis the various pharmacokinetic parameters are grossly altered. Clearance decreases, elimination half-life is substantially prolonged, and bioavailability more than doubles. In addition, the volume of distribution increases. Whereas renal disease has no impact on the pharmacokinetics of diltiazem and verapamil, elimination half-life of nifedipine increases in relation to the degree of renal impairment due to an increase in volume of distribution. Systemic clearance, however, remains unchanged. The data so far available indicate that the plasma concentrations of these drugs correlate with both their electrophysiological and haemodynamic effects. However, no effective therapeutic plasma concentration range has been firmly established. As reliable clinical end-points are available for dose titration of calcium antagonists, it is doubtful whether therapeutic drug monitoring will be of great value. Calcium antagonists are often administered in combination with a variety of other drugs. Thus, the potential for both pharmacodynamic and pharmacokinetic drug interaction exists. The interaction between digoxin and these drugs is of clinical importance. Verapamil and diltiazem cause a significant increase in plasma digoxin concentrations. In contrast, nifedipine does not lead to a significant increase in the plasma digoxin concentration. The mechanism responsible for this interaction is inhibition of both renal and non-renal digoxin clearance.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Verapamilmentioning

confidence: 70%

Clinical Pharmacokinetics of Verapamil, Nifedipine and Diltiazem

Echizen

Eichelbaum

1986

Clinical Pharmacokinetics

180

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“…However, the use of verapamil 10"" mol litre ' corresponds to the highest therapeutic concentration. Indeed, some studies suggest a therapeutic range of 150-500 mg ml" 1 [8][9][10][11]. The greatest concentrations are close to 10" 6 mol litre" 1 , but there is obviously an order of magnitude difference in the lower concentration.…”

Section: Discussionmentioning

confidence: 99%

“…However, the studies reported with verapamil on MHS human muscle have been poorly examined. To our knowledge, only one study reported that verapamil 8 x 10"' mol litre" 1 was effective in blocking halothane-induced contracture of MHS human muscle [7], but this concentration is much higher than that achieved clinically [8][9][10][11]. Verapamil is used widely in patients with cardiovascular disease [12] and some of these may undergo elective muscle biopsy for diagnosis of MH susceptibility.…”

mentioning

confidence: 99%

Clinical Concentrations of Verapamil Affect the in Vitro Diagnosis of Susceptibility to Malignant Hyperpyrexia

Adnet

Krivosic-Horber

Adamantidis

et al. 1990

British Journal of Anaesthesia

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We examined the effects of verapamil on the in vitro caffeine and halothane tests for malignant hyperpyrexia (MH) susceptibility. Ten consecutive MH-susceptible patients were investigated according to the protocol of the European MH group. Additional tests were carried out in the presence of verapamil 10(-6) mol litre-1. In four of the 10 patients, the halothane contracture response following pretreatment with verapamil was classified as positive to halothane. In contrast, in nine of the 10 patients, contracture tests of muscle in the presence of verapamil were classified as negative to caffeine. It is advised that verapamil should be discontinued before performing a contracture test.

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“…It is only more recently that its useful effect in chronic oral treatment has been demonstrated (Lewis et al, 1978;Midtbo & Hals, 1980;Anavekar et al, 1982;Doyle, 1983), and also shown with a slow release formulation (Schutz et al, 1982). The antihypertensive effect of verapamil has also been confirmed by studies using intraarterial monitoring .…”

Section: Calcium Antagonistsmentioning

confidence: 98%