Heimann G
Int J Biol Res Pregnancy. 1981;2(1):1-14.
During the perinatal period the problems of drug disposition are pronounced. The adaptation from the maternal-fetal unit to extrauterine life leads to alterations in drug absorption, distribution, metabolism, and renal elimination. Since both morphology and function of the alimentary tract changes, drugs are absorbed more slowly in the neonate than in older infants. Moreover, the serum protein binding of drugs is reduced in neonates. Consequently a measured plasma concentration may reflect a higher plasma/tissue level in the newborn as compared with adults. If the distribution volume of a drug corresponds to the total body water or extracellular water space, the dosage may be calculated in relation to the individual variations in the body surface area. But this procedure is not applicable for the newborn infant due to impaired metabolic functions of the liver and renal elimination mechanisms. The capacity of drug oxidation and glucuronidation is not fully developed in the neonate. Also glomerular filtration and tubular secretion are reduced during the first weeks of life. Therefore the elimination half-lives of many drugs are considerably prolonged in the newborn compared with that in older infants. As a consequence, individual therapeutic drug monitoring based on pharmacokinetic concepts and assisted by computer programs is becoming increasingly important.
在围产期，药物处置问题较为突出。从母胎单元向宫外生活的转变会导致药物吸收、分布、代谢及肾排泄发生改变。由于消化道的形态和功能均发生变化，新生儿药物吸收比大龄婴儿更慢。此外，新生儿药物的血清蛋白结合率降低。因此，与成人相比，测得的血浆浓度可能反映出新生儿体内更高的血浆/组织水平。如果一种药物的分布容积与总体水或细胞外水空间相对应，则可根据体表面积的个体差异来计算剂量。但由于肝脏代谢功能和肾脏排泄机制受损，该方法不适用于新生儿。新生儿药物氧化和葡萄糖醛酸化能力尚未完全发育。而且在出生后的头几周，肾小球滤过和肾小管分泌也会减少。因此，与大龄婴儿相比，许多药物在新生儿体内的消除半衰期会显著延长。因此，基于药代动力学概念并借助计算机程序进行的个体化治疗药物监测变得越来越重要。
