Nosocomial or late-onset
sepsis is a common complication among premature infants, with a frequency inversely correlated with
birth weight. Increased susceptibility to
infection is due in part to an immature humoral (antibody-mediated) immune response. This study investigated the pharmacokinetics (PKs) and safety of a donor-selected specific
intravenous immune globulin (
IVIG) preparation,
INH-A21 (
Veronate), for prevention of
sepsis in premature infants. Thirty-six infants weighing between 500 and 1,250 g during the first postnatal week were eligible to begin a series of up to four
intravenous infusions of 500 or 750 mg/kg of
body weight INH-A21. Blood samples were analyzed for
antibodies against the Ser-Asp
dipeptide repeat G (SdrG) and clumping
factor A (ClfA)
surface proteins of staphylococci. Sparse sampling and population PK analyses were performed to derive PK parameters. Following administration of the 500- and 750-mg/kg doses, the estimated average steady-state levels of anti-ClfA were 6.1 U/ml and 9.2 U/ml, respectively, and those of anti-SdrG were 5.2 U/ml and 7.7 U/ml, respectively. The elimination half-lives for anti-ClfA and anti-SdrG were 719 h and 701 h, respectively, and the clearances were 0.18 ml/h and 0.21 ml/h, respectively. In the final model, the values of the PK parameters were independent of gestational age. Both doses of
INH-A21 were well tolerated, and the safety profile was similar to those of other
IVIG preparations. These results suggest that a shorter dosing interval should be utilized between the first and second doses to achieve and maintain higher titers of anti-ClfA and anti-SdrG
antibodies. Further studies examining
INH-A21 for the prevention of late-onset
sepsis in infants within the weight range studied are warranted.