The pharmacokinetics of trinitroglycerin and its metabolites in patients with chronic stable angina

Hashimoto, Satoru; Yamauchi, Eiko; Kobayashi, Atsuko; Shigemi, Kenji; Yamashita, Tomomitsu; Tanaka, Yoshifumi

doi:10.1046/j.1365-2125.2000.00263.x

Cited by 3 publications

(1 citation statement)

References 3 publications

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“…Gibbs energies, enthalpies and entropies also have known [9]. Gas Chromatography is instrument that mostly used for identified nitroglycerin and its Derivatives [10][11][12][13][14][15]. Gas chromatography also can be used to quantify all product of nitration of glycerol [16].…”

Section: Introductionmentioning

confidence: 99%

Kinetic Modelling of Nitration of Glycerol: Three Controlling Reactions Model

Astuti¹,

Supranto²,

Rochmadi³

et al. 2014

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In the present study, a kinetic model of nitration between glycerol and nitric acid was developed. The presented model describes three controlling reactions model used elementary reactions consisting of three reversible reactions. The model utilizes first order reaction according to each reactant. The nitration of glycerol was modelled by fitting the kinetic model with 6 parameters, the rate constant at an average temperature and the activation energy. The reaction rate is assumed to be governed by three reactions, i.e. the formation of MNG (mononitroglycerin), the formation of DNG (dinitroglycerin) and the formation of TNG (nitroglycerin). The aim of this work is compare two models: seven controlling reactions model and three controlling reactions model. Two models have the similar trend. The three controlling reactions model gives better fit than seven controlling reactions model. The accuracy of three controlling reactions model is higher. The advantage of the seven controlling reactions model is this model can predict all products of nitration. So this model can be used at preliminary design plant. Three controlling reactions model can be used at next step, as design of reactor.

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Section: Introductionmentioning

confidence: 99%

Kinetic Modelling of Nitration of Glycerol: Three Controlling Reactions Model

Astuti¹,

Supranto²,

Rochmadi³

et al. 2014

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New developments in the management of preterm labor

Bukowski

Saade

2001

Seminars in Perinatology

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Clinical Pharmacokinetics and Pharmacodynamics of Glyceryl Trinitrate and its Metabolites

Hashimoto

Kobayashi

2003

Clinical Pharmacokinetics

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This review discusses the pharmacokinetics and pharmacodynamics of glyceryl trinitrate (nitroglycerin; GTN) pertinent to clinical medicine. The pharmacokinetics of GTN associated with various dose regimens are characterised by prominent intra- and inter-individual variability. It is, nevertheless, important to clearly understand the pharmacokinetics and characteristics of GTN to optimise its use in clinical practice and, in particular, to obviate the development of tolerance. Measurements of plasma concentrations of GTN and of 1,2-glyceryl dinitrate (1,2-GDN), 1,3-glyceryl dinitrate (1,3-GDN), 1-glyceryl mononitrate (1-GMN), and 2-glyceryl mononitrate (2-GMN), its four main metabolites, remain difficult and require meticulous techniques to obtain reliable results. Since GDNs have an effect on haemodynamic function, pharmacokinetic analyses that include the parent drug as well as the metabolites are important. Although the precise mechanisms of GTN metabolism have not been elucidated, two main pathways have been proposed for its biotransformation. The first is a mechanism-based biotransformation pathway that produces nitric oxide (NO) and contributes directly to vasodilation. The second is a clearance-based biotransformation or detoxification pathway that produces inorganic nitrite anions (NO(2) -). NO(2) - has no apparent cardiovascular effect and is not converted to NO in pharmacologically relevant concentrations in vivo. In addition, several non-enzymatic and enzymatic systems are capable of metabolising GTN. This complex metabolism complicates considerably the evaluation of the pharmacokinetics and pharmacodynamics of GTN. Regardless of the route of administration, concentrations of the metabolites exceed those of the parent compound by several orders of magnitude. During continuous steady-state delivery of GTN, for instance by a patch, concentrations of 1,2-GDN are consistently 2-7 times higher than those of 1,3-GDN, and concentrations of 2-GMN are 4-8 times higher than those of 1-GMN. Concentrations of GDNs are approximately 10 times higher, and of GMNs approximately 100 times higher, than those of GTN during sustained administration. The development of tolerance is closely related to the metabolism of GTN, and can be broadly categorised as haemodynamic tolerance versus vascular tolerance. Efforts are warranted to circumvent the development of tolerance and facilitate the use of GTN in clinical practice. Although this remains to be accomplished, it is likely that, in the near future, regimens will be developed based on a full understanding of the pharmacokinetics and pharmacodynamics of GTN and its metabolites.

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The pharmacokinetics of trinitroglycerin and its metabolites in patients with chronic stable angina

Cited by 3 publications

References 3 publications

Kinetic Modelling of Nitration of Glycerol: Three Controlling Reactions Model

Kinetic Modelling of Nitration of Glycerol: Three Controlling Reactions Model

New developments in the management of preterm labor

Clinical Pharmacokinetics and Pharmacodynamics of Glyceryl Trinitrate and its Metabolites

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