Vancomycin elimination in human infants with intrauterine growth retardation

Background: 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. Methods: 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 (V-d) and half-life (t(1/2)) for each subject. Pharmacokinetic profiles were compared between groups. Results: Overall, Cl, V-d 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 V-d, 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. Conclusions: 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 V-d is similar between SGA and AGA new-borns. 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.