CEFTAZIDIME PHARMACOKINETICS IN PRETERM INFANTS - EFFECTS OF RENAL-FUNCTION AND GESTATIONAL-AGE

Objective: The objectives of this study were (1) to determine the effe cts of gestational age on ceftazidime pharmacokinetics in the preterm infant, (2) to relate these effects to changes in glomerular filtratio n rate (GFR), and (3) to establish appropriate dosage recommendations for preterm infants on day 3 of life. Methods: Multiple-dose pharmacok inetics of ceftazidime (administered twice daily in a 25 or 50 mg/kg b ody weight intravenous dose) were evaluated in 136 preterm infants on day 3 of life. Blood samples were collected from an arterial catheter 0, 1/2, 1, 2, 4, 8, and 12 hours after the intravenous dose. An HPLC m ethod was used to determine ceftazidime concentrations in serum, The G FR was studied simultaneously by means of the 24-hour continuous inuli n infusion technique. Results: The total body clearance, volume of dis tribution, and elimination serum half-life of ceftazidime (mean +/- SD ) were 55.7 +/- 34.4 ml/hr (37.3 +/- 11.9 ml/hr/kg), 496 +/- 228 ml (3 50 +/- 96 ml/kg), and 6.95 +/- 2.32 hours, respectively. The mean +/- SD peak and trough levels were 114.9 +/- 39.4 and 33.9 +/- 17.8 mg/L. All infants had a serum trough level above 5 mg/L. Clearance and volum e of distribution of ceftazidime and GFR increased significantly with increasing gestational age, whereas serum trough levels and serum half -life of ceftazidime decreased significantly with increasing gestation al age. Ceftazidime clearance increased significantly with increasing GFR. Prenatal exposure to indomethacin resulted in significantly lower GFR values and ceftazidime clearances. Conclusions: Dosage recommenda tions for ceftazidime administration in preterm infants during the fir st week of life should be based on gestational age and GFR. Additional adjustments in dosage are indicated in preterm infants who are expose d prenatally to indomethacin.