CEFTAZIDIME PHARMACOKINETICS IN PRETERM INFANTS - EFFECT OF POSTNATALAGE AND POSTNATAL EXPOSURE TO INDOMETHACIN

1 The effects of postnatal age and postnatal exposure to indomethacin on the pharmacokinetic parameters of ceftazidime (CAZ) were investigat ed in 23 preterm infants (gestational age 28.7 +/- 1.7 weeks; weight 1 086 +/- 311 g) on day 3 and day 10 after birth. 2 CAZ (25 mg kg(-1)) w as administered by intravenous bolus injection. Blood samples were dra wn from an arterial catheter at 0, 0.5, 1, 2, 4, 8, and 12 h after the dose and CAZ concentrations in serum were determined by h.p.l.c. CAZ pharmacokinetics followed a one-compartment open model. 3 The glomerul ar filtration rate (GFR) of all infants was studied by means of the 24 h continuous inulin infusion technique. 4 The total body clearance of CAZ (34.7 +/- 9.2 vs 50.6 +/- 19.6 ml h(-1), P < 0.05; 30.7 +/- 5.9 v s 41.6 +/- 9.0 ml h(-1) kg(-1), P < 0.05) and GFR (0.72 +/- 0.11 vs 0. 91 +/- 0.15 ml min(-1), P < 0.05) increased, whereas the apparent volu me of distribution (425 +/- 147 vs 352 +/- 108 ml, P < 0.05; 363 +/- 5 9 vs 292 +/- 44 ml kg(-1), P < 0.005) and the elimination half-life (8 .7 +/- 2.8 vs 5.0 +/- 0.9 h, P < 0.005) decreased significantly betwee n day 3 and day 10 after birth. Clearance of CAZ increased with increa sing GFR (r = 0.81, P < 0.001), 5 In infants with postnatal exposure t o indomethacin the changes in CAZ pharmacokinetics were markedly reduc ed. 6 These results indicate that the dosage regimen of CAZ should be adjusted after the first week of life except in infants who were postn atally exposed to indomethacin.