Pharmacokinetics and antibacterial activity of daily gentamicin

Twenty full term neonates with suspected bacterial infection were randomly assigned to a once daily or a twice daily dosage regimen with gentamicin (4 mg/kg/day). Concomitantly all patients were treated with ampicillin (200 mg/kg/day). The gentamicin concentration time curves were analysed by an open two compartment model under steady state conditions on day 4 of treatment. The mean theoretical maximum serum concentration in the group taking gentamicin once daily (10.9 micrograms/ml) was significantly higher than in the group taking it twice daily (7.4 micrograms/ml). Potentially toxic serum concentrations were never reached. Mean trough concentrations were comparable in both groups (once daily 0.8 micrograms/ml; twice daily 1.0 micrograms/ml). Urinary alanine aminopeptidase excretion increased during and even two days after end of treatment in both groups without any significant differences. The results of the dynamic in vitro model revealed that both dosage schedules showed comparable bactericidal effects on pathogens inhibited by low concentrations of gentamicin like Escherichia coli and Staphylococcus aureus. However the once daily regimen was significantly superior in isolates with high minimal inhibitory concentrations.