Age dependence in capacity-limited jejunal decarboxylation of levodopa in rats

The extent of levodopa decarboxylation in a jejunal preparation permitting continuous in situ collection of the mesenteric blood was compared in rats 5 to 104 weeks old. The fraction of the absorbed amount that was metabolized (decarboxylated) in the jejunal segment was relatively high (approximately 0.7 to 0.8) in 9- to 15-week-old rats, whereas the fraction in relatively aged (52- and 104-week-old) and young (5- and 7-week-old) rats was considerably less (approximately 0.4 or less). These fractions were found to correlate better with the extent of relative contribution of the intestine in producing the overall first-pass effect of this drug after oral administration. In addition, kinetic studies on the jejunal metabolism of levodopa in vitro showed that a capacity-limited (i.e. saturable) decarboxylation rate was highest in 11-week-old rats. Therefore, the capacity-limited decarboxylation rate in the small intestine may be a determining factor in the age-dependent systemic availability of this drug when administered orally.