Approach to the pharmacokinetics of dl-7-3H-noradrenaline

Bufano, G.; Vaona, G; Starcich, R

doi:10.1007/bf00562432

Cited by 12 publications

(3 citation statements)

References 8 publications

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“…Although this approach has been attempted for the study of NE kinetics in humans ( 14,15), the early studies were limited by the lack of a sensitive and specific assay for plasma NE. Presently, methods to accurately measure plasma NE concentrations are readily available.…”

Section: Introductionmentioning

confidence: 99%

Norepinephrine metabolism in humans. Kinetic analysis and model.

Linares¹,

Jacquez²,

Zech³

et al. 1987

J. Clin. Invest.

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The present study was undertaken to quantify more precisely and to begin to address the problem of heterogeneity of the kinetics of distribution and metabolism of norepinephrine (NE) in humans, by using compartmental analysis. Steadystate NE specific activity in arterialized plasma during I3HINE infusion and postinfusion plasma disappearance of [3HINE were measured in eight healthy subjects in the supine and upright positions. Two exponentials were clearly identified in the plasma [HJNE disappearance curves of each subject studied in the supine (r = 0.94-1.00, all P < 0.01) and upright (r = 0.90-0.98, all P < 0.01) positions. A two-compartment model was the minimal model necessary to simultaneously describe the kinetics of NE in the supine and upright positions. The NE input rate into the extravascular compartment 2, estimated with the minimal model, increased with upright posture (1.87±0.08 vs. 3.25±0.2 pg/mm per Mi2, P < 0.001). Upright posture was associated with a fall in the volume of distribution of NE in compartment 1 (7.5±0.6 vs. 4.7+0.3 liters, P < 0.001), and as a result of that, there was a fall in the metabolic clearance rate of NE from compartment 1 (1.80±0.11 vs.1.21±0.08 liters/min per m=n, P < 0.001). We conclude that a two-compartment model is the minimal model that can accurately describe the kinetics of distribution and metabolism of NE in humans.

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Section: Introductionmentioning

confidence: 99%

Norepinephrine metabolism in humans. Kinetic analysis and model.

Linares¹,

Jacquez²,

Zech³

et al. 1987

J. Clin. Invest.

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“…This could be predicted from experiments where noradrenaline was injected iv into human volunteers, resulting in biological half-lives for noradrenaline of about 3 h (Búfano et al 1973). Within two to four half-lives (6-12 h) the excretion of catecholamines should thus have been within the normal range again.…”

Section: Discussionmentioning

confidence: 96%

Evidence for Extratumoural Storage of Catecholamines in Pheochromocytoma Patients

Hengstmann¹,

Dengler²

1978

Acta Endocrinologica

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Following the removal of a pheochromocytoma in three female patients the daily excretion of catecholamines and their metabolites was still considerably elevated for about one week. The excretion rates declined during this period with half-lives of 1.8 to 10.9 days for catecholamines and 2.1 to 4.7 days for metanephrines, vanilmandelic acid, and vanilglycol. The cumulative urinary excretion of catecholamines and their metabolites following surgical removal of the tumour was nearly as high as the catecholamine content of the pheochromocytomas. This large amount of catecholamines must have been located outside the tumour, most probably within the sympathetic nerve, where it is subject to release following physiological stimuli. Furthermore, this fact may provide an explanation for hypertensive crises in pheochromocytoma patients.In pheochromacytoma, hypertension may be either sustained or episodic. The classical hypertensive crisis may arise from a normotensive baseline or may occur in cases of sustained hypertension.In the sustained type of arterial hypertension increased levels of circulating catecholamines can provide a satisfactory aetiological explanation. However, it is less easy to explain hypertensive crisis in terms of current theories such as squeezing of the tumour, or on the basis of cyclic or episodic secretion. 589

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“…Although this half-time is not a simple index of a single removal mechanism (Shipley & Clark, 1972), the studies with desipramine and in patients with peripheral autonomic insufficiency indicate that neuronal uptake is its major determinant. An alternative explanation of the prolonged half-time, the presence of increased central pool size (Shipley & Clark, 1972) in the patients affected, was excluded by compartmental analysis adopting a two-pool open model (Bufano, Vaona & Starcich, 1973;Gibaldi & Perrier, 1975), which showed the central pool size to be unremarkable in hypertensive patients with prolonged half-time. Ghione, Palombo, Pellegrini, Fommei, Pilo & Donato (1978) have reported that removal of noradrenaline from the circulation is slowed in essential hypertension, and Gitlow, Mendlowitz, Kruk-Wilk, Wilk, Wolf & Naftchi (1964) have suggested previously that noradrenaline uptake might be abnormal in essential hypertension.…”

Section: Discussionmentioning

confidence: 99%

Determination of Noradrenaline Uptake, Spillover to Plasma and Plasma Concentration in Patients with Essential Hypertension

et al. 1980

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1. The rates of entry of noradrenaline to plasma and of removal of noradrenaline from plasma, and plasma noradrenaline concentration, were determined in normal subjects and in patients with essential hypertension. Neuronal uptake of noradrenaline was assessed from the plasma tritiated noradrenaline disappearance curve, after infusion to steady state. 2. Noradrenaline disappearance was biexponential. Rapid removal was dependent on neuronal uptake, being slowed if neuronal noradrenaline uptake was reduced, either by desipramine in normal subjects, or in patients with sympathetic nerve dysfunction (autonomic insufficiency). 3. In 10 of 41 hypertensive patients the t 1 1/2 similarly was prolonged, presumptive evidence of a defect in neuronal noradrenaline uptake. Endogenous noradrenaline escaping uptake after release, and spilling over into plasma, and plasma noradrenaline concentration, were increased in these patients. 4. Defective neuronal uptake of noradrenaline, by exposing adrenoreceptors to high local transmitter concentration, may be important in the pathogenesis of essential hypertension in some patients.

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Approach to the pharmacokinetics of dl-7-3H-noradrenaline

Cited by 12 publications

References 8 publications

Norepinephrine metabolism in humans. Kinetic analysis and model.

Norepinephrine metabolism in humans. Kinetic analysis and model.

Evidence for Extratumoural Storage of Catecholamines in Pheochromocytoma Patients

Determination of Noradrenaline Uptake, Spillover to Plasma and Plasma Concentration in Patients with Essential Hypertension

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