Changes in acetylator phenotype over the lifespan in the Wistar rat

Acetylation capacity during drug metabolism differs between species, gender and age groups.

The purpose of this work was to determine variations in the acetylating phenotype (AP), in a longitudinal study, as a function of growth and development.

Twenty male Wistar rats were studied. AP was determined on days 21, 48, 114, 180, 457 and 780 with oral doses of 30mg/kg of sulphadiazine (SDZ) by urine collection. The Schröeder and Vree methods were used to obtain SDZ concentrations, both acetylated and not acetylated. Rats were classified as slow or fast acetylators in accordance with previously validated metabolic indicators.

Of the 20 rats phenotyped at 21 and 48 days of age, 18 were slow and 2 were fast acetylators. As age and consequent growth progressed, changes in the expression of AP were registered. At 114 days, 16 rats were slow and 4 were fast acetylators; at 180 days, 12 were slow and 8 were fast; at 457 days, 6 were slow and 14 were fast; at 780 days, the 20 rats were fast acetylators. Slow acetylation predominates at younger ages.

The effect of growth and developmental progress on AP is evident and relates to previous reports of changes in AP, determined by age in animal and human models. The relevance of changes determined by growth and development should be considered in rational drug management.