THE EFFECT OF ASPHYXIA ON THE PHARMACOKINETICS OF CEFTAZIDIME IN THE TERM NEWBORN

The multiple-dose pharmacokinetics of ceftazidime (CAZ) (administered twice daily in a 50 mg/kg of body weight i.v. dose) were studied in 10 severely asphyxiated term infants with suspected septicemia on d 3 of life. Nine term infants with suspected septicemia but without asphyxi a served as controls. Blood samples were collected from an arterial ca theter at 0, 0.5, 1, 2, 4, 8, and 12 h after an i.v. bolus injection. A high performance liquid chromatography method was used to determine CAZ concentrations from serum. CAZ pharmacokinetics followed a one-com partment open model. The GFRs of all infants were simultaneously studi ed by means of the 24-h continuous inulin infusion technique. Eliminat ion serum half-life (5.86 +/- 1.13 h versus 3.85 +/- 0.40 h) and serum trough concentrations (46 +/- 14 mg/L versus 23 +/- 7 mg/L) of CAZ we re significantly (p < 0.001) increased in the asphyxiated newborn, whe reas total body clearance of CAZ (128.4 +/- 25.1 mL/h versus 205.7 +/- 55.4 mL/h), CAZ clearance per kg (40.9 +/- 6.1 mL/h/kg versus 60.8 +/ - 8.3 mL/h/kg), and the GFR expressed in mL/min (3.14 +/- 0.43 versus 4.73 +/- 0.89) were significantly (p < 0.001) decreased in the asphyxi ated newborn. We conclude that twice daily administration of 50 mg/kg of body weight CAZ given to asphyxiated term newborns in the first day s of life results in significantly higher serum trough levels in compa rison with control infants. The impaired CAZ clearance is a result of a significantly decreased GFR.