Thromboxane synthase inhibition: Implications for prostagland endoperoxide metabolism II testing the ‘redirection hypothesis’ in an acute intravenous challenge model

In the preceding paper we described the characterisation of an acute intravenous challenge model for the evaluation of the effects of thromboxane synthase inhibition (TXSI) on eicosanoid metabolism (1). Herein we describe the biochemical pharmacology of two TXSI and aspirin in this model. Both TXSI caused significant inhibition of plasma TXB₂ without elevation of 6-oxo-PGF_1α levels. Similar results were obtained when combined levels of 6-oxo-PGF_1α,13,14 dihydro 6-oxo-PGF_1α, 13,14 dihydro 6,15-dioxo-PGF_1α and 6-oxo-PGE₁ were measured as an index of PGI₂ biosynthesis (PGI₂m). Thus no evidence of redirection of PGH₂ to PGI₂ was found. experiments performed in serum gave an apparent stimulation of immunoreactive 6-oxo-PGF_1α following TXSI but RPHPLC analysis of extracted serum showed that this stimulation was accounted for by increase in a product co-eluting with [³H]PGF_2α. The implications of these findings in relation to TXSI and receptor antagonists are discussed.