Physiologically based kinetic modelling predicts the in vivo relative potency of riddelliine N-oxide compared to riddelliine in rat to be dose dependent.

ABSTRACT: Pyrrolizidine alkaloids (PAs) are toxic plant constituents occurring often in their N-oxide form. This raises the question on the relative potency (REP) values of PA-N-oxides compared to the corresponding parent PAs. The present study aims to quantify the in vivo REP value of riddelliine N-oxide compared to riddelliine using physiologically based kinetic (PBK) modelling, taking into account that the toxicity of riddelliine N-oxide depends on its conversion to riddelliine by intestinal microbiota and in the liver. The models predicted a lower C_max and higher T_max for the blood concentration of riddelliine upon oral administration of riddelliine N-oxide compared to the C_max and T_max predicted for an equimolar oral dose of riddelliine. Comparison of

SUBMITTER: Widjaja F 

PROVIDER: S-EPMC8748370 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature