Pharmacokinetic considerations in the adolescent: non-cytochrome P450 metabolic pathways

The non-oxidative metabolic reactions of methylation, acetylation, sulfation, glucuronidation, conjugation with amino acids (primarily with glycine), glutathione conjugation and esterase hydrolysis function to detoxify and enhance the elimination of drugs and pro-drugs, many of them as phase II reactions subsequent to oxidation. While the influence of maturation has been recognized in the development of hepatic oxidative capacity and specific pathways studied, considerably less attention has focused on the maturational effect in non-oxidative metabolism despite its role in drug deactivation, detoxification, and elimination. Consequently phase II metabolic capacities during adolescence remain primarily speculative. Conflicting data about one of these pathways, glucuronidation, suggest unexplored puberty- or gender-related phenomena influencing function in this system.