2001 Volume 16 Issue 1 Pages 22-26
Role of denitration in the pharmacokinetics (PK) and pharmacodynamics (PD) of organic nitrates was reviewed. The PK/PD relationship following i.v. bolus injection of stereoisomeric organic nitrates can be described using simple compartment and sigmoidal Emax models. Because the nitrates are prodrugs of nitric oxide and eliminate mainly as denitrated metabolites, both potency and duration of vasodilation depend on the extent of denitration. At present, the mechanism of nitrate tolerance remains poorly understood. However, the most of the important hypotheses are counter-regulative, so that the denitration may play an important role in the development of tolerance. It is desired to establish the PK/PD relationship of organic nitrates involving tolerance period and improve nitrate-therapy based on the relationship.
