Influence of posture on plasma nitroglycerin [letter]

Curry, Stephen H.; Kwon, HR

doi:10.1111/j.1365-2125.1985.tb02661.x

Cited by 20 publications

(7 citation statements)

References 15 publications

(7 reference statements)

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“…Parameters which influence dermal absorption are: a. Posture According to Heidemann et al (43) dorsal position did not lead to a significant increase in the nitroglycerin concentration in the plasma of 8 persons after dermal application of nitroglycerin (Nitroderm TTS 10, Ciba-Pharma) for a 12-hour period relative to normal daily activities in a standing position. On the other hand, dorsal position can cause up to three times higher concentrations of nitroglycerin in plasma compared to sitting position with sublingual administration (27). Lefebvre et al (61) found similar results after dermal application of nitroglycerin.…”

Section: Cutaneous Absorptionsupporting

confidence: 65%

Nitroglycerin [BAT Value Documentation, 1998]

Bolt¹

2012

The MAK‐Collection for Occupational Health and Safety

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Published in the series Biological Exposure Values for Occupational Toxicants and Carcinogens , Vol. 3 (1998) The article contains sections titled: Pharmacokinetics and Pharmacodynamics Kinetics Metabolism Dose‐dependency of the Effects of Nitroglycerin Pharmacodynamics Interaction Critical Toxicity Exposure and Effects Relationship between External and Internal Exposure Relationship between Internal Exposure and Effect Selection of the Indicators Nitroglycerin in Blood Glycerol‐1,2‐dinitrate and Glycerol‐1,3‐dinitrate in Blood Methodology Background Exposure Evaluation of the BAT Value Interpretation of the Data

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Section: Cutaneous Absorptionsupporting

confidence: 65%

Nitroglycerin [BAT Value Documentation, 1998]

Bolt¹

2012

The MAK‐Collection for Occupational Health and Safety

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“…Posture was found to markedly affect glyceryl trinitrate plasma concentrations after sublingual administration, with much higher concentrations in the supine than in the sitting position (Curry & Kwon 1985). One would expect a higher hepatic blood flow in the supine position, with a higher hepatic clearance of a high extraction drug such as glyceryl trinitrate.…”

Section: Other Methodological Considerationsmentioning

confidence: 97%

Clinical Pharmacokinetics of Glyceryl Trinitrate Following the Use of Systemic and Topical Preparations

Bogaert

1987

Clinical Pharmacokinetics

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Glyceryl trinitrate has been used for more than a century for the treatment of angina pectoris and, more recently, for the treatment of congestive heart failure. The introduction of transdermal delivery systems has renewed the controversy regarding the efficacy of the drug, mainly in the light of the development of tolerance. With concentrations of the order of 1 microgram/L or less, the measurement of glyceryl trinitrate in plasma is not easy: gas chromatography with electron capture detection has been used widely but recently gas chromatography-mass spectrometry has provided satisfactory results. Assay problems are most likely to be responsible for some of the unexpected results reported. Further factors which may confound the results of the study of plasma concentrations are the rapid metabolism of glyceryl trinitrate in blood in vitro, adsorption to containers and infusion sets, and the uptake and/or metabolism in vessel walls. From the intravenous infusion data, the large interindividual variability in plasma concentrations of glyceryl trinitrate is apparent. The plasma half-life is about 2 to 3 minutes; plasma clearance values reported vary from 216 to 3270 L/h, indicating extensive non-hepatic metabolism. With transdermal administration, mainly with the transdermal controlled delivery systems, plasma concentrations of glyceryl trinitrate appear to be maintained for up to 24 hours, with large interindividual variations. Despite the ability to maintain, for example with the transdermal delivery systems, relatively constant concentrations of glyceryl trinitrate, it has not been possible to find a relationship between plasma concentrations and pharmacological or clinical effects. This is in part due to the attenuation of the effects with time; from the available data it is clear that this attenuation occurs at a pharmacodynamic level (reflex adaptation and tolerance) and not at the pharmacokinetic level.

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“…The issue of plasma glyceryl trinitrate concentrations is further complicated, as posture (Curry & Kwon 1985) and exercise (Weber et al 1987) markedly influence these values. Also, following intravenous administration, a dose-related increase in plasma concentration with a hysteretic response was reported .…”

Section: Pharmacokineticsmentioning

confidence: 98%

Relationship of Pharmacokinetic and Pharmacodynamic Properties of the Organic Nitrates

Thadani

Whitsett

1988

Clinical Pharmacokinetics

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Glyceryl trinitrate (nitroglycerin), isosorbide dinitrate and isosorbide mononitrate are, in various formulations, available for clinical use. The pharmacokinetics of glyceryl trinitrate are complex and only 1% of the drug administered orally can be detected in the plasma due to a pronounced arteriovenous concentration gradient, hydrolysis in the blood, and rapid denitration in the liver. There is a poor and usually transient correlation between plasma concentrations and therapeutic effects, due in part to the complex pharmacokinetics of glyceryl trinitrate, but primarily due to development of tolerance during continuous administration, either via the intravenous or cutaneous route. Isosorbide dinitrate kinetics are complicated by its extensive metabolism into 2- and 5-mononitrates, which are pharmacologically active, and which also accumulate more than the parent drug during long term treatment. These facts, combined with development of tolerance during long term therapy, preclude the establishment of a concentration-response relationship. Isosorbide-5-mononitrate has ideal and dose-linear kinetics and is nearly 100% bioavailable after oral administration. However, tolerance develops during long term therapy, and therefore a relationship between plasma concentrations and clinical effects cannot be established. On the basis of available data, plasma concentrations of various nitrates do not reliably predict clinical effects.

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Influence of posture on plasma nitroglycerin [letter]

Cited by 20 publications

References 15 publications

Nitroglycerin [BAT Value Documentation, 1998]

Nitroglycerin [BAT Value Documentation, 1998]

Clinical Pharmacokinetics of Glyceryl Trinitrate Following the Use of Systemic and Topical Preparations

Relationship of Pharmacokinetic and Pharmacodynamic Properties of the Organic Nitrates

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