Back to Search
Start Over
In vivo antibacterial effects of simulated human serum profiles of once-daily versus thrice-daily dosing of amikacin in a Serratia marcescens endocarditis experimental model.
- Source :
-
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 1996 May; Vol. 40 (5), pp. 1164-9. - Publication Year :
- 1996
-
Abstract
- Once-daily dosage of aminoglycosides is currently under consideration. The lower toxicity of this regimen has been clearly established, but there are conflicting experimental and clinical data concerning its efficacy. It is inadvisable to optimize human therapy by extrapolation from experimental studies since animal and human pharmacokinetics differ. The simulation of human pharmacokinetics in experimental infectious models would seem to offer a more rational approach. We used computer-controlled infusion of amikacin at a variable flow rate to simulate human pharmacokinetics in a Serratia marcescens rabbit endocarditis model and to compare two therapeutic regimens (once-daily versus thrice-daily doses). The doses corresponded to simulations of 15 and 30 mg/kg of body weight per day in humans, and antibacterial activity was measured in vegetations (Veg) after 24 h of treatment. The results show that the dose corresponding to 15 mg/kg/day failed to produce a significant reduction of CFU (6.8 +/- 0.9 and 6.4 +/- 0.8 log10 CFU/g of Veg, respectively, for once-daily and thrice-daily doses versus 7.6 +/- 1.0 for controls). A significant reduction was observed only for the dose corresponding to 30 mg/kg/day in humans (5.2 +/- 1.5 and 5.4 +/- 1.1 log10 CFU/g of Veg, respectively, for the two regimens). With this model, the efficacy of amikacin was similar for both regimens after 24 h of treatment simulating human pharmacokinetics.
- Subjects :
- Amikacin blood
Amikacin pharmacokinetics
Animals
Drug Administration Schedule
Endocarditis, Bacterial blood
Female
Infusions, Intravenous
Models, Biological
Rabbits
Serratia Infections blood
Amikacin therapeutic use
Anti-Bacterial Agents therapeutic use
Endocarditis, Bacterial drug therapy
Serratia Infections drug therapy
Serratia marcescens drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0066-4804
- Volume :
- 40
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Antimicrobial agents and chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 8723459
- Full Text :
- https://doi.org/10.1128/AAC.40.5.1164