The Non-Linear Child: Ontogeny, Isoniazid Concentration, and NAT2 Genotype Modulate Enzyme Reaction Kinetics and Metabolism.

ABSTRACT: N-acetyltransferase 2 (NAT2) catalyzes the acetylation of isoniazid to N-acetylisoniazid. NAT2 polymorphism explains 88% of isoniazid clearance variability in adults. We examined the effects of clinical and genetic factors on Michaelis-Menten reaction kinetic constants of maximum velocity (V_max) and affinity (K_m) in children 0-10years old. We measured the rates of isoniazid elimination and N-acetylisoniazid production in the blood of 30 children. Since maturation effects could be non-linear, we utilized a pharmacometric approach and the artificial intelligence method, multivariate adaptive regression splines (MARS), to identify factors predicting NAT2 V_max and K_m by examining clinical, genetic, and laboratory factors in toto. Isoniazid concentrat

SUBMITTER: Rogers Z 

PROVIDER: S-EPMC5049930 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature