We prospectively studied the pharmacokinetic parameters of vancomycin
in premature neonates given vancomycin according to a dosage protocol
developed in our neonatal unit. Study infants were administered vancom
ycin according to four postconceptional age (PCA) groups: (0) 18 mg/kg
every 36 h for PCA < 27 weeks; (I) 16 mg/kg every 24 h for PCA 27-30
weeks; (II) 18 mg/kg every 18 h for PCA 31-36 weeks; and (III) 15 mg/k
g every 12 h for PCA greater than or equal to 37 weeks, Pharmacokineti
c parameters were calculated from peak and trough serum vancomycin con
centrations at steady state. Results in 44 infants (PCA, 27-14 weeks)
showed that our dosage regimen achieved target peak serum vancomycin c
oncentrations in 64% of neonates in Groups I-III, although it tended t
o undershoot the target trough concentrations. Volume of distribution
(Vd), normalized for body weight, remained constant throughout the PCA
range, with a mean value of 0.56 L/kg, whereas absolute clearance (r
= 0.81) and normalized clearance (r = 0.48) increased with PCA (p < 0.
005). The increase in clearance with PCA is associated with a greater
elimination rate constant and shorter half-life. Vancomycin therapy ca
n be initiated in a standard fashion according to our protocol or by i
ndividualizing the dosage regimen based on a Vd of 0.56 L/kg and clear
ance estimated from the infant's body weight and PCA groups.