The pharmacokinetics of ranitidine in critically ill children are variable. The description of ranitidine's pharmacokinetics and pharmacodynamics in this study may used to design an initial ranitidine dosage regimen that targets a gastric pH > or =4. Thereafter, gastric pH should be monitored and the dose of ranitidine adjusted accordingly.

leucine uptake and protein synthesis in the near-term ovine fetus: relation to fetal behavioral state. Am J Physiol Regul Integr Comp Physiol 284: R200-R207, 2003; 10.1152/ ajpregu.00190.2002-Behavioral/sleep state activity may impact on synthetic processes within the brain, thus accounting for the developmental change in such activity and suggesting a role in the brain's growth and development. We have therefore determined the cerebral uptake of leucine and [ 14 C]leucine during continuous tracer infusion as measures of leucine metabolism in relation to behavioral state activity, as well as the regional flux of leucine into brain tissue in the ovine fetus near term. The cerebral fractional protein synthetic rate and the absolute protein synthetic rate averaged ϳ20%/day and ϳ1 g/day, respectively, as measured for the whole brain, which is considerably higher than anticipated protein accretion and indicates a high rate of protein turnover with protein synthesis closely linked to protein degradation. Measures of protein synthesis were significantly higher in the pituitary gland, which may be attributed to the active synthesis and export of peptide hormones from this region. Cerebral leucine and [14 C]leucine uptakes averaged ϳ630 and ϳ1,000 nmol ⅐ 100 g Ϫ1 ⅐ min Ϫ1 , with the latter higher than leucine unidirectional flux and thus supporting a degree of leucine oxidation by the brain. Cerebral leucine metabolism as studied was affected by behavioral state activity, with uptake measurements for both leucine and [ 14 C]leucine significantly increased during the high-voltage electrocortical/non-rapid eye movement state by 1.7-fold and 2.8-fold, respectively, indicating that protein synthesis and degradation must also be increased at this time, and supporting a role for behavioral state activity in the brain's growth and development. brain development; leucine metabolism CEREBRAL PROTEIN SYNTHESIS has been studied during brain growth and development, both pre-and postnatally in sheep (1, 24) and postnatally in the rat (6, 26), because proteins are integral components of structural elements in brain tissue and with the metabolism of brain protein directly related to maturational events (26). Initial study in the near-term ovine fetus by Schaefer and Krishnamurti (24) using a tyrosine isotopic-dilution technique showed high rates of cerebral protein synthesis with a fractional protein synthetic rate between 14 and 37%/day and an absolute rate of synthesis of ϳ1 g/day. A subsequent study in fetal sheep by Abrams and colleagues (1) using [14 C]leucine autoradiography reported a rate of leucine incorporation into brain protein of ϳ5 nmol ⅐ g Ϫ1 ⅐ min Ϫ1 , with an overall increase through the latter part of gestation and into the early postnatal period likely reflecting cerebral myelination. Postnatal studies in rats have similarly shown high rates of brain protein synthesis during early development, with peak values occurring shortly after birth and gradually decreasing thereafter (6, 26). While high rates of cerebral pr...

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