Pharmacokinetics and pharmacodynamics of nifedipine infusion in normal volunteers.

Walley, Tom; Heagerty, AM; Woods, K. L.; Bing, R. F.; Pohl, Jürgen; Barnett, David

doi:10.1111/j.1365-2125.1987.tb03103.x

Cited by 22 publications

(16 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Nifedipine usually shows no marked antihypertensive eŠect in normal individuals, because the diastaltic sympathicotonia through pressoreceptor with decreases of peripheral arterial resistance induces the increases of heart rate, and prevents blood pressure decreases. 20) However, there have been reports [21][22][23][24][25][26][27][28] that nifedipine signiˆcantly reduced the blood pressure by oral and sublingual administration and that the serum nifedipine concentration was correlated with the antihypertensive eŠect in normal individuals. In our study, also, the serum concentration was correlated with blood pressure, especially DBP, by each administration method.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Method for Nifedipine Administration for a Rapid Onset of Clinical Effect: A Clinical Study in Normal Volunteers.

2001

View full text Add to dashboard Cite

Nifedipine is frequently used for patients who require an immediate reduction of blood pressure elevated temporarily by various administration techniques including sublingual route without administrating intravenous infusion of vasodilator. A cross-over clinical study was conducted to investigate the optimal administration metho of nifedipine for rapid management of hypertension. Four method of administering 10 mg nifedipine (the capsule was bitten and swallowed, sublingually with a hole in it or the contents administered orally or intranasally with a syringe) were evaluated with regarded e‹cacy, safety, and usefulness in 6 normal volunteers. Systolic and diastolic blood pressures were correlated with the nifedipine serum concentration in each method. Nifedipine pharmacokinetic parameters diŠered among the 4 administration methods. Nifedipine was absorbed rapidly by not only intestinal mucosa but also the nasal or oral mucosa. The pharmacological eŠect of intranasal or sublingual administration was superior. However, mint oil which is present in nifedipine capsules stimulates nasal mucosa when administered intranasally. For clinical usage, nifedipine capsules in which a hole is made with a needle, administered sublingually, can be eŠectively and safely used for rapid management of systemic hypertension.

show abstract

Section: Discussionmentioning

confidence: 99%

Evaluation of the Method for Nifedipine Administration for a Rapid Onset of Clinical Effect: A Clinical Study in Normal Volunteers.

2001

View full text Add to dashboard Cite

show abstract

“…The effects were rather small in these normotensive volunteers, and the extent of interand intra-subject variability of the haemodynamic effects was too large to allow pharmacodynamic-pharmacokinetic modelling in the majority of the subjects. Also some haemodynamic activity of the vehicle cannot be ruled out (Walley et al, 1987). After oral administration the effects were even less and, because the study was not placebo controlled, it can only be concluded that there are no major differences between the haemodynamic effects of nitrendipine when given as a tablet as compared with an Osmet formulation.…”

Section: Calculationsmentioning

confidence: 99%

“…The side-effects were remarkably severe and consistent for one subject, whereas for the other subjects side-effects were less frequent and less severe. The local irritation after intravenous administration which is probably caused by the vehicle (Walley et al, 1987) could not completely be prevented by simultaneous infusion of normal saline, but no signs of thrombophlebitis were observed.…”

Section: Calculationsmentioning

confidence: 99%

Oral absorption profile of nitrendipine in healthy subjects: a kinetic and dynamic study.

Soons

Boer

Brummelen

et al. 1989

Brit J Clinical Pharma

View full text Add to dashboard Cite

1 In nine healthy male subjects the kinetics of nitrendipine were assessed after i.v. administration and its absorption profile was studied when given by a tablet formulation and by an osmotic pumping device (Osmet) with a zero-order in vitro release of 2.62 ± 0.19 mg h-' for 13 h.2 Plasma concentrations of nitrendipine and its pyridine metabolite, heart rate and blood pressure were determined at regular intervals after drug administration. 3 After i.v. nitrendipine, the plasma concentration declined triexponentially with a mean terminal elimination half-life of 11.7 ± 5.4 h. The mean systemic plasma clearance was 1.47 ± 0.22 1 min-1. 4 Administration of the Osmet resulted in a relatively smooth plasma concentrationtime profile in comparison with the tablet. The mean plateau concentration was 2.63 + 1.31 ng ml-1 and the duration of this plateau was 10.7 ± 3.2 h. The intake of food gave rise to a transient increase of the plasma concentration of both nitrendipine and its pyridine metabolite.5 The mean bioavailability of nitrendipine from the Osmet (8.2 ± 1.6%) was lower than from the tablet (11.1 ± 4.5%), which is probably due to release of nitrendipine in lower parts of the G.I. tract where absorption is not or less possible. 6 Intravenous administration caused a transient decrease in DBP of 26 ± 4%, accompanied by a maximal reflex tachycardia of 46 ± 17%. No clear haemodynamic effects were observed after oral administration. The Osmet produced less side-effects (headache) than the tablet.

show abstract

“…Although the pharmacokinetics and pharmacodynamics of nifedipine have been characterized extensively in adults (6)(7)(8)(9), only a few studies to date have evaluated the hemodynamic responses in a pediatric population (3)(4)(5), and pharmacokinetic studies in this population are completely lacking. The objectives of this study were to determine the pharmacokinetic properties of nifedipine in children with BPD and pulmonary artery hypertension after the administration of a single oral dose of the drug, and to evaluate the relationship between plasma nifedipine concentrations and the acute responses.…”

mentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Nifedipine in Children with Bronchopulmonary Dysplasia and Pulmonary Hypertension

et al. 1991

View full text Add to dashboard Cite

ABSTRACT. The pharmacokinetics and associated pharmacodynamics of nifedipine were studied in nine children aged 5 to 68 mo with bronchopulmonary dysplasia and pulmonary artery hypertension after a single oral dose of 1.44 tLmol/kg (0.5 rug/kg). In the cardiac catheterization laboratory, hemodynamic measurements were made in duplicate just before the nifedipine dose and at 5 min and 0.5 and 1.0 h after the dose. The plasma nifedipine concentration was measured by HPLC at each of the above times and at 2.5, 4.0, 6.0, and 8.0 h after the dose. The mean (± SD) maximum plasma concentration and the time to maximum plasma concentration were 243.4 ± 194.5 nmol/L and 1.0 ± 0.8 h, respectively. The mean area under the plasma concentration-time curve was 761 ± 509 nmol-h/ L. The mean elimination rate constant and t,;, were 0.456 ± 0.194 h-I and 1.8 ± 0.8 h, respectively. Nifedipine caused a significant (p ::s 0.05) reduction in the mean pulmonary artery pressure by 5 min and in the mean pulmonary vascular resistance index and mean aortic pressure by 30 min, and these reductions remained significant through the J-h measurement interval. The magnitude of acute hemodynamic response correlated closely with the plasma nifedipine concentrations. No significant change occurred in the mean arterial oxygen saturation or cardiac index during the study period. The percentage changes from baseline in the mean pulmonary artery pressure and mean pulmonary vascular resistance index were approximately double the percentage change in the mean aortic pressure, suggesting that nifedipine had some degree of selective impact on the pulmonary vascular bed. Based on these results, an initial oral maintenance regimen of 1.44 tLmol/kg (0.5 mg/kg) every 6 h would be needed for this patient population. If the safety and efficacy after chronic therapy can also be shown, nifedipine may prove to be an important therapeutic addition to the management of children with bronchopulmonary dysplasia and pulmonary hypertension.

show abstract

Pharmacokinetics and pharmacodynamics of nifedipine infusion in normal volunteers.

Cited by 22 publications

References 26 publications

Evaluation of the Method for Nifedipine Administration for a Rapid Onset of Clinical Effect: A Clinical Study in Normal Volunteers.

Evaluation of the Method for Nifedipine Administration for a Rapid Onset of Clinical Effect: A Clinical Study in Normal Volunteers.

Oral absorption profile of nitrendipine in healthy subjects: a kinetic and dynamic study.

Pharmacokinetics and Pharmacodynamics of Nifedipine in Children with Bronchopulmonary Dysplasia and Pulmonary Hypertension

Contact Info

Product

Resources

About