Stewart C F, Hampton E M
Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee, Memphis 38163.
Clin Pharm. 1987 Jul;6(7):548-64.
Maturational changes in the physiologic processes that govern drug disposition in pediatric patients are described, and evaluation of data from pediatric drug studies is discussed. Gastrointestinal absorption depends on gastric pH, gastric emptying time, intestinal transit time, and gastrointestinal enzymatic activity; the overall effect of age-related alterations in these variables is poorly understood. Maturational changes in the skin affect percutaneous absorption. Distribution of drugs is affected by alterations in vascular perfusion, body composition, tissue binding, and plasma protein binding. For most water-soluble drugs, volume of distribution is increased in neonates. Age-related changes in biotransformation are complex because the rate of development of phase 1 and phase 2 metabolic pathways varies and metabolic pathways may be induced by in utero exposure to inducing agents. For most drugs, biotransformation is decreased in the neonate, increases from one to five years of age, and decreases after puberty to adult values. The kidneys of neonates are inefficient at drug elimination, leading initially to prolonged elimination half-lives of many drugs. Clearance of some drugs may be greater in infants than in older children and adults because of disproportionate development of renal filtration and secretion in relation to reabsorption. Few data on maturational changes in physiologic processes that affect drug disposition are available for any one drug in a specific pediatric population. In the development of research protocols, careful attention should be paid to the design limitations of published studies.
描述了小儿患者体内药物处置相关生理过程的成熟变化，并讨论了儿科药物研究数据的评估。胃肠道吸收取决于胃内pH值、胃排空时间、肠道转运时间和胃肠道酶活性；这些变量随年龄变化的总体影响尚不清楚。皮肤的成熟变化会影响经皮吸收。药物分布受血管灌注、身体组成、组织结合和血浆蛋白结合变化的影响。对于大多数水溶性药物，新生儿的分布容积会增加。生物转化的年龄相关变化很复杂，因为I相和II相代谢途径的发育速度不同，且代谢途径可能因子宫内接触诱导剂而被诱导。对于大多数药物，新生儿的生物转化能力降低，1至5岁时增加，青春期后降至成人水平。新生儿的肾脏在药物消除方面效率低下，最初导致许多药物的消除半衰期延长。由于肾滤过和分泌相对于重吸收的发育不成比例，一些药物在婴儿体内的清除率可能高于大龄儿童和成人。对于特定儿科人群中的任何一种药物，关于影响药物处置的生理过程成熟变化的数据都很少。在制定研究方案时，应仔细关注已发表研究的设计局限性。
