Enteral absorption and bioavailability in children in relation to age.

Abstract

There is little information about enteral drug absorption during development compared to that about drug distribution, metabolism and excretion. Therefore, the bioavailability, i.e. the amount and rate of absorption of various drugs (sulfonamides, phenobarbital, digoxin, β-methyldigoxin) and test substances (D(+)-xylose, L(+)-arabinose) was investigated in 580 children using pharmacokinetic methods. The amounts of the drugs absorbed, determined by Dost's law of corresponding areas, showed no age dependence. But the rate of absorption, ka, calculated from the concentration time curves using a digital approximation procedure (RIP), is low at the time of birth and reaches adult values after the neonatal period. This phenomenon is identical for all of the substances tested. A prolonged gastric emptying time in the neonate does not seem to be responsible for the delayed absorption since the lagtime is not related to age. Stimulation of intestinal motility with metoclopramide increases the absorption rates, both in neonates and older children, but the age dependent differences remain. Using various dosages of L(+)-arabinose the parameters of the saturation kinetics could be determined. In neonates Vmax values are significantly lower than in older children. Similarly, the affinity constant\(\mathop K\limits^ \star\) indicates a decreased capacity of enteral absorption in neonates compared with older children. Bioavailability data from adults cannot be accepted without further investigation since the rate of enteral drug absorption depends on age.