Neonates, especially preterms, are known to have low glomerular filtration
rates (GFR). This may result in elevated trough concentrations during
multiple administration of aminoglycosides (AGs), potentially leading to
nephro- and ototoxic reactions. The once-daily administration (q.d.) of
AGs has been shown to be equally or better tolerated in adults and children
than the conventional schedules (twice daily, b.i.d.; thrice daily,
t.i.d.), while offering potential pharmacodynamic and nursing advantages.
No data, however, are available for neonates. As a consequence, this pilot
study was conducted in order to assess the tolerance of the once-a-day
administration of amikacin in comparison with the twice daily dose regimen,
in relation to the pharmacokinetics of the drug under these two
schedules. 22 Male neonates (gestational age ≥ 34 weeks; postnatal age ≤ 2
days) were randomized to receive amikacin (AK) (15 mg/kg/day) q.d. (n =
10) or b.i.d. (n = 12) together with ampicillin (50 mg/kg/12 h). AK plasma
levels were measured at days 1,3,5 and 7 of treatment just before the next
dose (trough level) and 1 h after completion of infusion (peak level) and
after 3 and 6 h only at day 1. Due to the small size of the samples, no
difference in efficacy could be assessed and was not the aim per sc. Glomerular
dysfunction was assessed by creatinine clearance, and tubular
injuries by the urinary excretion of proteins (retinol binding protein, ß2-
microglobulin, clara cell protein (PI) and microalbumin), enzymes (Nacetyl-
ß-D-glucosaminidase, alkaline phosphatase, alanine aminopeptidase,
and y-glutamyltransferase), and total phospholipids (TPL) in urine.
Ototoxicity was assessed by brainstem auditory evoked potentials
(BAEPs) at days 0, 3 and 9 of therapy. Eight healthy neonates served as
controls. All patients showed a normal and similar increase of GFR during
the first postnatal days. Proteinuria did not increase, but enzymuria and
TPL increased significantly during the treatment in both AK groups without
significant difference between groups. BAEPs at day 9 were not significantly
different between treated and untreated patients.
We conclude from this pilot study that, in the absence of more toxicity,
the q.d. administration of AK in neonates of ≥ 34 weeks of gestational age
may be recommended over its bid schedule in view of its potential advantages.
