NEPHROTOXICITY, HIGH-FREQUENCY OTOTOXICITY, EFFICACY AND SERUM KINETICS OF ONCE VERSUS THRICE DAILY DOSING OF NETILMICIN IN PATIENTS WITH SERIOUS INFECTIONS

The effect of dosing regimen on nephrotoxicity, high frequency ototoxi city, efficacy and serum kinetics was studied in a prospective, random ised clinical study. Therapy was started with total daily doses of 6 m g/kg given once (od) or thrice (tid) daily to 56 and 57 patients, resp ectively. Subsequent doses were adjusted according to serum levels. No major differences in toxicity or efficacy were noticed between od and tid regimens: clinical failures occurred in two and two patients, fou r and five patients suffered from a decrease of greater than or equal to 20 dB at least unilaterally at one frequency between 8 and 18 kHz, six and seven patients had a > 25 mu mol/L or > 25% increase in serum creatinine, respectively. Serum creatinine or creatinine clearance did not change significantly during either therapy. Major differences bet ween the two study groups were limited to pharmacokinetic parameters. Od dosing resulted in higher peak (mean of 21.6 vs 7.2mg/L) and lower trough levels (0.5 vs 1.4mg/L). Half-lives of netilmicin determined be tween 1 and 8h increased significantly during therapy with tid (from a mean of 2.75 to a mean of 3.33 h, P<0.01) but not significantly with od (rise from 2.8 to 3.03 h). Much longer half-lives were determined b etween 8 and 24 h in the od group (mean of 5.7 h, P<0.01). In conclusi on, only minimal differences in toxicity and efficacy were observed. T heir clinical relevance appears to be minimal.