Dev Pharmacol Ther 1993;20(3-4):220-30

Once-a-day administration of amikacin in neonates: assessment of nephrotoxicity
and ototoxicity.

Langhendries JP, Battisti O, Bertrand JM, Francois A, Darimont J, Ibrahim S,
Tulkens PM, Bernard A, Buchet JP, Scalais E

Department of Paediatrics, Children's Hospital, St-Joseph-Esperance-Rocourt,
Clinique St-Vincent, Belgium.

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 > or = 34 weeks;
postnatal age < or = 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 se.
Glomerular dysfunction was assessed by creatinine clearance, and tubular
injuries by the urinary excretion of proteins (retinol binding protein, beta
2-microglobulin, clara cell protein (P1) and microalbumin), enzymes
(N-acetyl-beta-D-glucosaminidase, alkaline phosphatase, alanine aminopeptidase,
and gamma-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 > or = 34 weeks of
gestational age may be recommended over its bid schedule in view of its
potential advantages.

Publication Types:
Clinical trial
Randomized controlled trial

PMID: 7828457, UI: 95129386