Pharmacokinetics and pharmacodynamics of isradipine (PN 200-110) in young and elderly patients

Chellingsworth, M.; Willis, J. V.; Jack, David; Kendall, M. J.

doi:10.1016/0002-9343(88)90192-1

Cited by 18 publications

(10 citation statements)

References 14 publications

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“…The plasma concentrations of isradipine here were in accordance with other results [11,12], demonstrating absorption and stable plasma levels within 30 min of administration.…”

Section: Discussionsupporting

confidence: 92%

Renal effects of the new calcium channel blocking drug isradipine

Krämer

Häussler

Ress

et al. 1990

Eur J Clin Pharmacol

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Summary. The acute effect of a single oral dose of isradipine 5 mg on blood pressure, renal haemodynamics, electrolyte excretion and plasma renin activity was studied in 10 healthy males.Isradipine did not produce a significant change in systolic or diastolic blood pressure, and glomerular filtration rate, renal plasma flow, renal vascular resistance, and urinary albumin excretion remained constant. There was a marked natriuretic and diuretic effect about 1-3 h after isradipine. Plasma renin activity showed a slight, insignificant increase i h after dosing. Uric acid clearance and 132-microglobulin excretion showed no significant changes, despite an increase in sodium clearance, suggesting an additional mechanism of action other than the proximal tubular natriuretic effect of isradipine in normotensive volunteers.

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“…The plasma concentrations of isradipine here were in accordance with other results [11,12], demonstrating absorption and stable plasma levels within 30 min of administration.…”

Section: Discussionsupporting

confidence: 92%

Renal effects of the new calcium channel blocking drug isradipine

Krämer

Häussler

Ress

et al. 1990

Eur J Clin Pharmacol

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“…Several studies on the pharmacokinetics of isradipine after oral administration have been published (Tse & Jaffe 1987;Clifton et al 1988;Chandler et al 1988;Schran et al 1988;Chellingsworth et al 1988;Shenfield et al 1990;Christensen et al 1993), (table 3), while until now only one study has evaluated the kinetic parameters after intravenous ad- ministration (Carrara et al 1994). No study with a similar design has been dealing with bioavailability.…”

Section: Discussionmentioning

confidence: 99%

Bioavailability and Pharmacokinetics of Isradipine after Oral and Intravenous Administration: Half‐Life Shorter than Expected?

Christensen¹,

Antonsen.

Simonsen

et al. 2000

Pharmacology & Toxicology

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Isradipine is a calcium channel-blocking agent of the dihydropyridine type, used in the treatment of hypertension. A terminal half-life of 8-9 hr has been reported, in several pharmacokinetic studies after oral administration of isradipine. In a yet unpublished study a much shorter half-life was observed, and the present trial was therefore conducted in order to estimate the half-life after intravenous administration of isradipine. The bioavailability was estimated as well. In a randomised cross-over design ten healthy young volunteers were given either isradipine orally or an intravenous infusion. The two study periods were separated by at least 3 days. Blood samples for measurement of isradipine concentration were collected for 10-12 hr after administration and half-life and bioavailability were estimated. Mean terminal half-life after intravenous administration was calculated to be 2.8 hr, and the bioavailability to be 0.28. None of the 10 subjects suffered from side effects. In the present intravenous study the half-life of isradipine seems to be of much shorter than demonstrated in previous oral studies.Isradipine, a dihydropyridine calcium channel-blocking agent, elicits potent vasodilation of the systemic vascular bed without causing any significant cardiodepression (van Wijk 1989). Clinical experience has shown that isradipine administered orally in doses from 1.25 to 2.5 mg b.i.d. as tablets or 5.0 mg once daily in a sustained release formulation has an effect on blood pressure equal to that of other antihypertensive drugs (Fitton & Benfield 1990;Christensen et al. 1991).The terminal half-life of isradipine after oral studies is reported to be about 8.8 hr (Fitton & Benfield 1990). In yet unpublished studies we have observed a significantly shorter half-life (2.5 hr) following intravenous administration of isradipine to patients with pregnancy-induced hypertension. To elucidate if this apparent discrepancy was caused by methodological differences (oral versus intravenous administration) or due to physiological differences induced by pregnancy we conducted this trial to evaluate isradipine kinetics after intravenous infusion and oral administration to healthy volunteers. Materials and MethodsTen healthy normotensive volunteers, (3 women, 7 men) mean age 24.2 years, and mean weight 71.9 kg were included in the study (table 1). All the subjects had serum concentration values of haemoglobin, potassium, sodium, creatinine and liver enzymes within normal range. below 110/60 mmHg, if blood had been donated within the last 2 months, or if drugs of any kind were used. All volunteers gave written informed consent, and the study was approved by the Local Ethics Committee, the Danish Health authorities and was performed in agreement with the Helsinki declaration.Design. In a randomised cross-over fashion the volunteers were given isradipine as an infusion as well as orally. Half of them started with an infusion of isradipine followed by oral treatment, while the other half were given isradipine orally fol...

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“…In elderly patients, no major dose adjustments are required, at least in the "young elderly" with a mean age of 66 to 72 years [77,79]. Nonetheless, blood levels tend to be higher in the elderly [72], as might be expected from their lower cardiac output.…”

Section: Isradipinementioning

confidence: 99%

Calcium channel antagonists: part VI: Clinical pharmacokinetics of first and second-generation agents

Opie

1989

Cardiovasc Drug Ther

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A survey of the pharmacokinetic properties of the three prototypical calcium antagonist agents shows that they have in common a very high rate of hepatic first-pass metabolism with, in the case of verapamil and diltiazem, the formation of an active metabolite that affects the dose during chronic therapy. Therefore, the major factor altering the pharmacokinetic properties and the dose of the drug required is the capacity of the liver to metabolize the drug, which in turn depends on the hepatic blood flow and the activity of the hepatic metabolizing systems. Hence liver disease, a low cardiac output, and coadministration of certain drugs inducing or inhibiting the hepatic enzymes, all indirectly affect the pharmacokinetic properties of the calcium antagonists. There are also other potential drug interactions of a kinetic or dynamic nature that may arise. In general, renal disease has little effect on the pharmacokinetics of calcium antagonists.

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Pharmacokinetics and pharmacodynamics of isradipine (PN 200-110) in young and elderly patients

Cited by 18 publications

References 14 publications

Renal effects of the new calcium channel blocking drug isradipine

Renal effects of the new calcium channel blocking drug isradipine

Bioavailability and Pharmacokinetics of Isradipine after Oral and Intravenous Administration: Half‐Life Shorter than Expected?

Calcium channel antagonists: part VI: Clinical pharmacokinetics of first and second-generation agents

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