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Ceftazidime pharmacokinetics in preterm infants: Effects of renal function and gestational age
Author(s) -
Anker John N.,
Schoemaker Rik C.,
Hop Wim C. J.,
Heijden Bert J.,
Weber Allan,
Sauer Pieter J. J.,
Neijens Herman J.,
Groot Ronald
Publication year - 1995
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/0009-9236(95)90021-7
Subject(s) - ceftazidime , pharmacokinetics , medicine , renal function , volume of distribution , gestational age , anesthesia , urology , pregnancy , genetics , bacteria , pseudomonas aeruginosa , biology
Objective The objectives of this study were (1) to determine the effects of gestational age on ceftazidime pharmacokinetics in the preterm infant, (2) to relate these effects to changes in glomerular filtration rate (GFR), and (3) to establish appropriate dosage recommendations for preterm infants on day 3 of life. Methods Multiple‐dose pharmacokinetics of ceftazidime (administered twice daily in a 25 or 50 mg/kg body weight intravenous dose) were evaluated in 136 preterm infants on day 3 of life. Blood samples were collected from an arterial catheter 0, ½, 1, 2, 4, 8, and and 12 hours after the intravenous dose. An HPLC method was used to determine ceftazidime concentrations in serum. The GFR was studied simultaneously by means of the 24‐hour continuous inulin infusion technique. Results The total body clearance, volume of distribution, 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 (350 ± 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 volume 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 gestational age. Ceftazidime clearance increased significantly with increasing GFR. Prenatal exposure to indomethacin resulted in significantly lower GFR values and ceftazidime clearances. Conclusions Dosage recommendations for ceftazidime administration in preterm infants during the first week of life should be based on gestational age and GFR. Additional adjustments in dosage are indicated in preterm infants who are exposed prenatally to indomethacin. Clinical Pharmacology & Therapeutics (1995) 58 , 650–659; doi: