J Antimicrob Chemother 1991 May;27 Suppl C:49-61

Pharmacokinetic and toxicological evaluation of a once-daily regimen versus
conventional schedules of netilmicin and amikacin.

Tulkens PM

Laboratoire de Chimie Physiologique, Universite Catholique de Louvain, Brussels,
Belgium.

The safety and pharmacokinetics of netilmicin (6.6 mg/kg) and amikacin (14.5
mg/kg) once daily (od) have been compared to their corresponding conventional
schedules thrice daily (tid), and twice daily (bd), in patients (20 per group)
suffering from pelvic inflammatory disease. Sensitive criteria of early renal
and auditory alterations, namely urinary excretion of phospholipids and
audiometry over a wide frequency range (0.25-18 kHz), respectively, were used.
The first criterion (phospholipiduria) was validated by an animal study which
demonstrated that rats receiving poly-L-aspartic acid, which protects against
gentamicin-induced nephrotoxicity, are also protected against renal
phospholipidosis and phospholipiduria caused by this antibiotic. On that basis,
netilmicin od was better tolerated than netilmicin tid. Amikacin caused less
phospholipiduria than netilmicin, and, given od, resulted in little increase
over baseline (95% CI, 95-147% increase). Reduction in threshold by greater than
or equal to 15 dB for frequencies between 10-18 kHz occurred in nine of 19
patients receiving netilmicin tid compared with three or four of 19 or 20
patients treated with netilmicin od or amikacin (od or bd). However, changes at
lower frequencies (0.25-8 kHz) were infrequent with all regimens (from 0/19 to
2/20). In conclusion, these very sensitive tests of nephro- and oto-toxicity
suggest that od dosing of amikacin or netilmicin is, if anything, safer than bd
or tid dosing.

Publication Types:
Clinical trial
Controlled clinical trial

PMID: 1856146, UI: 91310540