This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The recognition that pain is experienced by neonates has led to the more common use of morphine in neonatal intensive care units. There are data demonstrating a developmental pattern in the metabolism and pharmacokinetics (PK) of morphine that needs to be considered in its use. This information, however, has not been translated into a morphine dosage schedule for neonates that recognizes differences in both drug disposition and action. The purpose of this study is to 1) evaluate the relationship of developmental stage (defined by both gestational and postnatal age) to UGT2B7 activity (as measured by the M3G/morphine ratio and M6G/morphine ratio in blood and urine); 2) evaluate the relationship of UGT2B7 genetic variability to the M6G/morphine ratio and the M3G/morphine ratio in both blood and urine; 3) evaluate the relationship of glomerular filtration rate to M6G/morphine ratio, M3Gmorphine ratio, and morphine concentrations in both blood and urine; 4) evaluate the relationship of -opioid receptor variability and catechol-O-methyltransferase gene (COMT) variability to clinical response following administration of morphine; and 5) develop a population PK/PD model of morphine dosing based on gestational age, postnatal age, glomerular filtration rate, and genetic variability in UGT2B7, in the -opioid receptor, and in COMT.
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