Plasma nitroglycerin levels after sublingual, oral and topical administration.

Blumenthal, H. P.; Fung, Ho‐Leung; McNiff, Edward F.; Yap, S.K.

doi:10.1111/j.1365-2125.1977.tb00703.x

Cited by 67 publications

(10 citation statements)

References 3 publications

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“…"glL (Blumenthal et al 1977;Chu et al 1984;Magometschnigg et al 1983;MaierLenz et al 1980), while others found concentrations well over 1 ILgfL (Armstrong et al 1980a;Bashir et al 1982;Iafrate et al 1983;Imhof et al 1980;Wei & Reid 1979). The type of ointment used, the amount applied and the surface area and duration of application vary, but it is impossible to determine which of these factors is responsible for the differences in plasma concentrations seen from study to study, and systematic studies are scarce.…”

Section: Ointmentsmentioning

confidence: 91%

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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Section: Ointmentsmentioning

confidence: 91%

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

Bogaert

1987

Clinical Pharmacokinetics

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“…Maximum plasma concentrations are reached within a few minutes after sublingual administration (7,16,22,50,63,102). The nitroglycerin concentrations in plasma rapidly decrease again, however.…”

Section: Sublingual Absorptionmentioning

confidence: 95%

“…Data in the literature differ widely (19). For example, in one study the plasma concentration of nitroglycerin after sublingual administration of 0.3 mg nitroglycerin was about 1 ng/ml (16), while in another it was less than 1 ng/ml after administration of 1.6 mg nitroglycerin (50). The bioavailability of nitroglycerin after sublingual administration is on average 36 % (79).…”

Section: Sublingual Absorptionmentioning

confidence: 99%

“…According to Noonan and Benet (81) bioavailability is less than 1 %. Clinical investigations show that after ingestion, nitroglycerin cannot be detected in plasma or the concentrations are very low (16,81,83,106). Metabolites such as glycerol dinitrate are, however, detectable (57,83 (91) found that the glycerol dinitrate levels were up to 10 times higher than the nitroglycerin levels after oral and dermal administration of nitroglycerin.…”

Section: Ingestionmentioning

confidence: 99%

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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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“…Data following slow release oral preparations of GTN or cutaneously absorbed preparations are scanty. A previous investigation by Blumenthal and co-workers (Blumenthal et al, 1977) compared plasma GTN levels in one subject following sublingual (0.3 mg) oral (6.5 mg) and topical (16 mg) GTN administration. These workers found markedly lower plasma GTN concentrations after each of the preparations than were found in the present study.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic studies of various preparations of glyceryl trinitrate.

Bashir¹,

Mj²,

Henderson³

1982

Brit J Clinical Pharma

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1 The pharmacokinetics and pharmacodynamics of five pharmaceutical preparations of glyceryl trinitrate (GTN) have been studied in six healthy volunteers. 2 Peak plasma GTN levels of 1.4 + 0.1 ng/ml were achieved at 3 min after sublingual administration (0.5 mg); 2.8 + 0.6 ng/ml and 2.5 + 0.3 ng/ml at 2 h and 4 h after Nitrocontin (6.4 mg) and Sustac (6.4 mg) respectively; 2.7 + 0.1 ng/ml and 2.5 ± 0.2 ng/ml at 30 min after the cream (23 mg) and ointment (35 mg) respectively. 3 The mean times to reach half peak plasma GTN levels were 4.2 + 0.7 min after sublingual GTN, 6.5 + 0.9 h after Nitrocontin, 4.1 + 0.7 h after Sustac, 46.1 + 10.2 min after the ointment and 50.2 ± 39.2 min after the cream. 4 Plasma nitrate (NO3) levels were undetectable after sublingual administration; peak NO3 levels were 0.48 + 0.03 ,ug/ml at 4 h after Nitrocontin, 0.45 + 0.02 ,ug/ml at 6 h after Sustac, 0.68 + 0.04 ,g/ml at 6 h (end of study) after the ointment and 0.63 ,ug/ml at 4 h after the cream. 5 Plasma nitrite (NO2) was undetectable after sublingual GTN and peak NO2 levels were 0.48 ± 0.04 ,ug/ml at 2 h after Nitrocontin, 0.48 + 0.02 ,ug/ml at 2 h after Sustac, 0.69 ± 0.02 jug/ml at 1 h after the ointment and 0.64 + 0.02 ,ug/ml at 1 h after the cream. 6 Blood pressure (BP) declined throughout the 11 min of the study after sublingual GTN but did not change significantly after Nitrocontin or Sustac. After the ointment and the cream BP fell to the lowest level 30-60 min after administration and remained low throughout the 6 h of the study. 7 Heart rate (HR) increased to a maximum 5 min after sublingual administration with no significant increase after Nitrocontin or Sustac. After the ointment and the cream HR increased gradually to a maximum 30-60 min after administration remaining high throughout the rest of the study.

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Plasma nitroglycerin levels after sublingual, oral and topical administration.

Cited by 67 publications

References 3 publications

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

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

Nitroglycerin [BAT Value Documentation, 1998]

Pharmacokinetic studies of various preparations of glyceryl trinitrate.

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