Plasma Concentration—Effect Relationships of Intravenous and Extended-Release Oral Felodipine in Hypertensive Patients

Blychert, Eva; Hedner, Thomas; Dahlöf, Carl; Elmfeldt, Dag

doi:10.1097/00005344-199003000-00013

Cited by 32 publications

(16 citation statements)

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“…For more detailed information, the reader is referred to several recently published reviews [5,[9][10][11][12][13]. Publications on individual agents, for example, nisoldipine [14][15][16][17][18], amlodipine [13], and felodipine [19][20][21], may also be consulted.…”

Section: Properties Of Second-generation Calcium Channel Blockersmentioning

confidence: 99%

Pharmacological aspects of calcium channel blockers

Scholz

1997

Cardiovasc Drug Ther

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Calcium channel blockers (CCBs) inhibit voltage-dependent L-type calcium channels. This leads to vascular smooth muscle relaxation and negative inotropic and chronotropic effects in the heart. The latter are counteracted in vivo by a vasodilatation-triggered, baroreceptor-mediated reflex increase in sympathetic tone, resulting in indirect cardiostimulation. The mean vascular/cardiac effect ratios of the first-generation CCBs-verapamil, nifedipine, and diltiazem-are relatively low and amount to approximately 3, 10, and 3, respectively. The pharmacokinetic properties of verapamil, nifedipine, and diltiazem are similar. The drugs are almost completely absorbed after oral administration, but their bioavailability is reduced because of first-pass hepatic metabolism. The onset of action of verapamil, nifedipine, and diltiazem, at least in immediate-release formulations, is relatively fast (0.5-2 hours), and their elimination half-lives range from 2 to 7 hours. The second-generation CCBs (e.g., amlodipine, felodipine, and nisoldipine) have a slower onset of action (due to either intrinsic properties of the drug or a slow-release formulation), a longer duration of action, and greater vascular/cardiac effect ratios. These features may provide therapeutic benefits, for example, a less pronounced increase in sympathetic tone and reflex tachycardia, and reduced likelihood of negative inotropic effects. These agents can therefore probably be used in patients with left ventricular dysfunction.

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Section: Properties Of Second-generation Calcium Channel Blockersmentioning

confidence: 99%

Pharmacological aspects of calcium channel blockers

Scholz

1997

Cardiovasc Drug Ther

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“…21 (6) 1991 Clearance values are lower and the t' l2' Y is increased in comparison with healthy young volunteers (table II). At steady-state, both AUC and Cmax were unaltered with plain tablets (Edgar et al 1987c), but with ER tablets an increase of 40% in Cmax with no change in AUC was noted (Blychert et al 1990b). The clinically important difference between a single dose and steady-state is a 3-to 4-fold increase in Cmin (Bengtsson- Hasselgren et al 1989;Edgar et al 1987c;Hedner et al 1987b) as a consequence of the long t'l2'Y' In 2 large clinical studies with felodipine ER in patients with hypertension, the increase in the morning plasma concentrations (24h after the last dose) was linear to the given dose (Faison 1991;Tibblin 1989).…”

Section: Hypertensionmentioning

confidence: 99%

Felodipine Clinical Pharmacokinetics

Dunselman

Edgar

1991

Clinical Pharmacokinetics

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Absorption of felodipine is rapid and complete. A pronounced first-pass metabolism results in a bioavailability of 15%, irrespective of the oral formulation used. The peak plasma concentrations and area under the plasma concentration-time curve are linearly related to the dose. The variability in plasma concentrations is wide, and individualization of the dosage is recommended. Plasma felodipine concentrations are increased in the elderly, and in patients with congestive heart failure or liver cirrhosis; in these patients felodipine should be started at a low dosage. Food intake has no clinically significant effect on felodipine absorption. Serum digoxin concentrations are increased by felodipine in plain tablet form, but not when it is administered as extended release tablets. Activators, inducers and inhibitors of the cytochrome P450 system affect the plasma concentrations of felodipine. No displacement reactions with high affinity protein binding drugs have been observed. There is a significant correlation between plasma concentration and haemodynamic effect. The mean elimination half-life of 24h together with the extended release formulation of felodipine favours once-daily dosage in patients with hypertension.

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“…Felodipine is a 1,4-dihydropyridine calcium antagonist for which a plasma concentration-effect relationship has been established (Blychert et al, 1990;Edgar et al, 1987). In man felodipine undergoes extensive firstpass metabolism (Edgar et al, 1985a;RegArdh et al, 1989), the major metabolic step involving oxidative degradation by cytochrome P450 IIIA of the 1.4-dihy- dropyridine to the inactive dehydrofelodipine ( Figure 1, Baarnhielm et al, 1984;Hoffman & Andersson, 1984).…”

Section: Introductionmentioning

confidence: 99%

A population study of the pharmacokinetics of felodipine.

Blychert

Edgar

Elmfeldt

et al. 1991

Brit J Clinical Pharma

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1 The pharmacokinetics of felodipine was studied after continuous oral administration of 5 or 10 mg conventional tablets to a population of 140 male and female Caucasian subjects, of which 67 were hypertensive patients and 73 were healthy volunteers. In addition, 42 of these individuals received felodipine intravenously. 2 With increasing age the area under the felodipine plasma concentration vs time curve (AUC), the maximum plasma concentration (Cmax), and the terminal elimination halflife of felodipine increased, while the plasma clearance of felodipine decreased. The bioavailability and steady state volume of distribution and the time to Cmax were not consistently influenced by age. 3 The ratio of the AUC of the primary pyridine metabolite of felodipine and that of unchanged drug decreased with increasing age. 4 Neither Cmax, AUC nor the half-life of felodipine were related to body mass index. 5 The distribution of AUC for felodipine, as well as the ratio of the AUC of the first metabolite to that of unchanged felodipine, was unimodal. Thus, the presence of a sizable group of individuals, with a clinically significant different metabolism of 1,4-dihydropyridine due to genetic factors is unlikely. 6 The pharmacokinetics of felodipine did not seem to differ between hypertensive patients and healthy volunteers, when adjusted for age. Neither was there a difference between patients taking 3-adrenoceptor antagonists and those who did not. 7 As a group the elderly had higher total concentrations of unchanged felodipine in plasma compared with younger individuals. The variation in plasma concentrations of felodipine between individuals is, however, only partially explained by age. In clinical practice this emphasizes the need for dose titration of felodipine.

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Plasma Concentration—Effect Relationships of Intravenous and Extended-Release Oral Felodipine in Hypertensive Patients

Cited by 32 publications

References 0 publications

Pharmacological aspects of calcium channel blockers

Pharmacological aspects of calcium channel blockers

Felodipine Clinical Pharmacokinetics

A population study of the pharmacokinetics of felodipine.

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