Clinical Pharmacokinetics and Pharmacodynamics of Glyceryl Trinitrate and its Metabolites
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Clin Pharmacokinet 2003; 42 (3): 205-221 0312-5963/03/0003-0205/$30.00/0 © Adis International Limited. All rights reserved.
Clinical Pharmacokinetics and Pharmacodynamics of Glyceryl Trinitrate and its Metabolites Satoru Hashimoto and Atsuko Kobayashi Department of Intensive Care and Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Contents Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Analytical Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1 Measurement of Glyceryl Trinitrate and Its Metabolites . . . . . . . . . 1.2 Sample Protection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Nonenzymatic Metabolic Pathways . . . . . . . . . . . . . . . . . . . . 2.2 Enzymatic Metabolic Pathways . . . . . . . . . . . . . . . . . . . . . . 3. Clinical Pharmacokinetics and Pharmacodynamics . . . . . . . . . . . . . 3.1 Pharmacokinetics in Humans . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Pharmacokinetics of Metabolites . . . . . . . . . . . . . . . . . . . . . 3.3 Other Factors Influencing Pharmacokinetics and Pharmacodynamics 3.3.1 Patch Size and Renewal . . . . . . . . . . . . . . . . . . . . . . . . 3.3.2 Physical Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3.3 Temperature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3.4 Posture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3.5 Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Pharmacokinetic and Pharmacodynamic Modelling and Mitigation of Tolerance . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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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-glycer
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