Pharmacokinetics of once-daily dosing of gentamicin in neonates.
In a prospective, randomized trial of once-daily versus twice-daily intravenous or intramuscular dosing with gentamicin, 11 neonates received 5.0 mg/kg once daily and 15 received 2.5 mg/kg twice daily for 2 ro 3 days. The once-daily intravenous dosing group and the twice-daily intravenous or intramuscular dosing group, respectively, had mean steady-state gentamicin peak concentrations of 10.7 versus 6.6 micrograms/ml (p < 0.05), 6-hour postdosing concentrations of 4.7 versus 2.8 micrograms/ml (p < 0.05), trough concentrations of 1.7 versus 1.7 micrograms/ml, elimination half-life of 8.8 versus 5.4 hours (p < 0.05), and volume of distribution at steady state of 0.67 versus 0.46 L/kg. No nephrotoxic effects were identified in any group. Once-daily gentamicin therapy with 5.0 mg/kg in neonates achieves peak serum levels that are more suitable for optimal bacterial killing than those which traditional regimens achieve. Similar trough levels suggest that even larger doses and longer dosing intervals may be ideal in term neonates.
Hayani
K C
KC
Department of Pediatric, University of Illinois, Chicago 60612-7324, USA.
Hatzopoulos
F K
FK
Frank
A L
AL
Thummala
M R
MR
Hantsch
M J
MJ
Schatz
B M
BM
John
E G
EG
Vidyasagar
D
D
D000667:Ampicillin / Q000008:administration & dosage / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001424:Bacterial Infections / Q000188:drug therapy; D003404:Creatinine / Q000097:blood / Q000652:urine; D004334:Drug Administration Schedule; D005839:Gentamicins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects; D010406:Penicillins / Q000008:administration & dosage / Q000627:therapeutic use; D011446:Prospective Studies; D001613:beta 2-Microglobulin / Q000652:urine
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D010406:Penicillins; D001613:beta 2-Microglobulin; D000667:Ampicillin; D003404:Creatinine