Pentaerythritol tetranitrate and metabolites in rat plasma

Intact pentaerythritol (PE) tetranitrate and all seven of its metabolites were present in blood withdrawn from the hearts of rats dosed by gavage with 14-C-PE tetranitrate (10 mg/kg). The plasma half-life (T 1/2) of PE tetranitrate was 2 hours which is far longer than the rat T 1/2 values of all other organic nitrates in clinical use. PE trinitrate, the obligatory metabolite of PE tetranitrate now in clinical trial, establishes much higher plasma levels and has a longer T 1/2 (3 hours) than its parent drug. PE trinitrate glucuronide acts as a reservoir for its aglycone and remains in blood for 48 hours after PE tetranitrate administration.