Frattarelli Daniel A C, Ergun Hakan, Lulic-Botica Marianne, Lehr Victoria Tutag, Aranda Jacob V
Division of Clinical Pharmacology, Children's Hospital of Michigan, Detroit, MI, USA.
Pediatr Infect Dis J. 2005 Nov;24(11):979-83. doi: 10.1097/01.inf.0000186283.95728.34.
Intrauterine growth retardation (IUGR) results in substantial decrease in nephron number and renal and hepatic organ mass in experimental animals and newborn infants. Because the liver and the kidneys are the major organs for drug biotransformation and elimination, any decrease in their size and function may lead to impaired metabolism and elimination of drugs in newborns with IUGR. Our objective was to test the hypothesis that IUGR results in prolonged renal elimination of vancomycin in newborns.
Small for gestational age (SGA) infants (n = 20) were matched with appropriate for gestational age (AGA) infants (n = 123). Steady state peak and trough serum concentrations were used to calculate vancomycin clearance (Cl), volume of distribution (Vd) and half-life (t(1/2)) for each subject. Pharmacokinetic profiles were compared between groups.
Overall, Cl, Vd and t(1/2) of vancomycin were the same between groups. However, stratification showed decreased Cl in those SGA versus AGA newborns 3-4 weeks old and in those newborns with a postconceptional age of 27-29 weeks. There was no difference in Vd, normalized for weight, between SGA and AGA babies. The half-life of vancomycin was similar across most groups but was prolonged in SGA newborns aged 3-4 weeks.
Vancomycin Cl differs between SGA and AGA newborns. This difference is greatest early in life and normalizes between groups after the fourth week of life or after 29 weeks postconceptionally. Normalized Vd is similar between SGA and AGA newborns. The elimination of vancomycin is comparable between SGA and AGA infants, except before the fifth week of life, when SGA newborns may eliminate the drug more slowly. Specific vancomycin dose recommendations for SGA versus AGA neonates may therefore be justified during the first month of life.
宫内生长受限（IUGR）会导致实验动物和新生儿的肾单位数量以及肾脏和肝脏器官质量大幅减少。由于肝脏和肾脏是药物生物转化和消除的主要器官，其大小和功能的任何降低都可能导致IUGR新生儿的药物代谢和消除受损。我们的目的是检验IUGR会导致新生儿万古霉素肾脏清除时间延长这一假设。
将小于胎龄（SGA）婴儿（n = 20）与适于胎龄（AGA）婴儿（n = 123）进行匹配。使用稳态峰浓度和谷浓度来计算每个受试者的万古霉素清除率（Cl）、分布容积（Vd）和半衰期（t(1/2)）。比较两组之间的药代动力学特征。
总体而言，两组之间万古霉素的Cl、Vd和t(1/2)相同。然而，分层分析显示，3 - 4周龄的SGA新生儿与AGA新生儿以及孕龄为27 - 29周的新生儿中Cl降低。SGA和AGA婴儿之间，经体重标准化后的Vd没有差异。大多数组中万古霉素的半衰期相似，但3 - 4周龄的SGA新生儿半衰期延长。
SGA和AGA新生儿的万古霉素Cl不同。这种差异在生命早期最大，在出生后第四周或孕龄29周后两组之间趋于正常。SGA和AGA新生儿经标准化后的Vd相似。SGA和AGA婴儿之间万古霉素的消除情况相当，除非在出生后第五周之前，此时SGA新生儿可能消除药物的速度更慢。因此，在出生后的第一个月内，针对SGA与AGA新生儿制定特定的万古霉素剂量建议可能是合理的。
