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Nephrotoxicity, high frequency ototoxicity, efficacy and serum kinetics of once versus thrice daily dosing of netilmicin in patients with serious infections


Blaser, J; Simmen, H P; Thurnheer, U; König, C; Lüthy, R (1995). Nephrotoxicity, high frequency ototoxicity, efficacy and serum kinetics of once versus thrice daily dosing of netilmicin in patients with serious infections. Journal of Antimicrobial Chemotherapy, 36(5):803-814.

Abstract

The effect of dosing regimen on nephrotoxicity, high frequency ototoxicity, efficacy and serum kinetics was studied in a prospective, randomised clinical study. Therapy was started with total daily doses of 6 mg/kg given once (od) or thrice (tid) daily to 56 and 57 patients, respectively. 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, four and five patients suffered from a decrease of ≥20 dB at least unilaterally at one frequency between 8 and 18 kHz, six and seven patients had a >25 μmol/L or >25% increase in serum creatinine, respectively. Serum creatinine or creatinine clearance did not change significantly during either therapy. Major differences between the two study groups were limited to pharmacokinetic parameters. Od dosing resulted in higher peak (mean of 21.6 vs 7.2 mg/L) and lower trough levels (0.5 vs 1.4mg/L). Half-lives of netilmicin determined between 1 and 8 h 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 between 8 and 24 h in the od group (mean of 5.7 h, P<0.01). In conclusion, only minimal differences in toxicity and efficacy were observed. Their clinical relevance appears to be minimal

Abstract

The effect of dosing regimen on nephrotoxicity, high frequency ototoxicity, efficacy and serum kinetics was studied in a prospective, randomised clinical study. Therapy was started with total daily doses of 6 mg/kg given once (od) or thrice (tid) daily to 56 and 57 patients, respectively. 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, four and five patients suffered from a decrease of ≥20 dB at least unilaterally at one frequency between 8 and 18 kHz, six and seven patients had a >25 μmol/L or >25% increase in serum creatinine, respectively. Serum creatinine or creatinine clearance did not change significantly during either therapy. Major differences between the two study groups were limited to pharmacokinetic parameters. Od dosing resulted in higher peak (mean of 21.6 vs 7.2 mg/L) and lower trough levels (0.5 vs 1.4mg/L). Half-lives of netilmicin determined between 1 and 8 h 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 between 8 and 24 h in the od group (mean of 5.7 h, P<0.01). In conclusion, only minimal differences in toxicity and efficacy were observed. Their clinical relevance appears to be minimal

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:1 January 1995
Deposited On:12 Oct 2018 07:39
Last Modified:24 Nov 2018 02:58
Publisher:Oxford University Press
ISSN:0305-7453
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/jac/36.5.803
Related URLs:https://www.swissbib.ch/Search/Results?lookfor=nationallicenceoxford101093jac365803 (Library Catalogue)

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