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Influence of early malnutrition on drug metabolism and effect

Male Sprague-Dawley rats were raised in litters of 10 (controls, C) and 18 (malnourished, M) until 21 days of age (weaning). Total body and liver weights were decreased by 30% in the M group. As a consequence liver weight remained at the same percentage of body weight (4.89 ± 0.1) as in the controls (4.75 ± 0.2). The microsomal components of the electron transport chain for oxidative pathways were similar in both groups. Metabolism for several different oxidative substrates (aminopyrine, aniline, and benzpyrene) was increased significantly in liver homogenates in the M group. Since drug metabolism is the most important determinant of drug effect, hexobarbital was used in correlative in vivo studies. The duration of sleep (the major action of hexobarbital) was surprisingly longer in the M animals (160 ± 9 minutes) than in the controls (112 ± 6 minutes) at a dose of 100 mg/kg. Since hexobarbital metabolism was not decreased in the M group these findings strongly suggest that brain sensitivity is altered. This may have important consequences for drug usage in malnourished children.