ABSTRACT
Multidose pharmacokinetics of vancomycin were studied in 15 infants with gestational age less than 36 weeks and suspected or confirmed Staphylococcus epidermidis infections. Postconceptional age (PCA) at the time of the study ranged from 26 to 44 weeks. Vancomycin individual doses ranged from 6.7 to 10.6 mg/kg and were infused over 60 min. Five postinfusion samples were obtained in 13 infants, while 4 samples were obtained in 2 patients. Vancomycin pharmacokinetic parameters were determined by fitting the data to a two-compartment model using a weighted least-squares nonlinear regression method. Mean vancomycin body clearance (CL), volume of distribution (Vdss) and terminal elimination half-life were 1.37 ml/min, 0.58 liters and 5.6 h, respectively. When standardized for patient weight, the CL and Vdss values were 1.07 ml/min/kg and 0.48 liters/kg, respectively. The CL (ml/min/kg) was strongly inversely correlated with the serum creatinine (r = -0.82), while a weaker but significant association was noted with PCA (r = 0.41). These data suggest that in sick infants, in addition to the PCA, serum creatinine should be considered when determining the initial vancomycin dosing regimen.
Subject(s)
Creatinine/blood , Infant, Premature/metabolism , Staphylococcal Infections/drug therapy , Vancomycin/pharmacokinetics , Body Weight , Female , Gestational Age , Humans , Infant , Infant, Newborn , Infusions, Intravenous , Male , Staphylococcus epidermidis , Vancomycin/administration & dosage , Vancomycin/therapeutic useABSTRACT
Studies performed in patients with cystic fibrosis (CF) have suggested altered pharmacokinetic parameters for aminoglycosides. Specifically, increased plasma clearance (Cl) of aminoglycosides and increased apparent volume of distribution have been noted. In the present study, tobramycin Cl is determined by both serum concentration data and direct renal clearance (Clren). Tobramycin Clren appeared to be directly correlated to the measured creatinine clearance (Clcr) (r = 0.93, p less than 0.01). The tobramycin Cl, by both methods of determination, was not elevated in comparison to the Clcr or expected values for patients without the disease. These results appear to corroborate a recent study in which the renal and plasma Cl of gentamicin was measured in patients with mild-to-moderate CF and were not noted to be elevated. It is suggested that standard doses of tobramycin be used initially in patients with mild-to-moderate CF with dosage adjustment based on serum concentration data to achieve the desired goals.
