Pharmacokinetics and pharmacodynamics of NTBC (2‐(2‐nitro‐4‐fluoromethylbenzoyl)‐1,3‐cyclohexanedione) and mesotrione, inhibitors of 4‐hydroxyphenyl pyruvate dioxygenase (HPPD) following a single dose to healthy male volunteers

Abstract

NTBC and mesotrione are both inhibitors of HPPD, although the magnitude and duration of their effect on tyrosine concentrations are very different. When normalized for dose, the extent of the induced tyrosinaemia after administration of NTBC and over the duration of these studies, was approximately 400 fold greater than that following administration of mesotrione. The persistent and significant effect on HPPD following administration of NTBC make it suitable for the treatment of patients with hereditary tyrosinaemia type 1 (HT-1), whilst the minimal and transient effects of mesotrione minimize the likelihood of a clinical effect in the event of systemic exposure occurring during occupational use.