Age and the pharmacokinetic-pharmacodynamic relationship of phenobarbital in rats: "pseudo"-longitudinal vs cross-sectional study design.

In a previous study, an apparent age-related increase in brain sensitivity to the anesthetic effect of phenobarbital was observed in BN/BiRij rats. However, since this study was conducted according to a cross-sectional design, the observed change could, in principle, also have been the result of a cohort effect. The purpose of the present investigation was to exclude the role of such a cohort effect by adopting a "pseudo"-longitudinal study design. In this design 45 animals out of one cohort were reserved, and one subgroup was investigated at five ages (7, 14, 21, 29, and 34 months). A decrease in the anesthetic threshold dose of phenobarbital was found during aging, which appeared to be due mainly to an increase in the brain sensitivity. It is concluded that the previously observed increase in brain sensitivity is indeed the result of the aging process rather than a cohort effect.