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[Renal accumulation of gentamicin in rabbits]
Abstract:
Renal accumulation, nephrotoxicity and serum concentration of gentamicin (GM) by intravenous infusion were studied in rabbits, and compared with those observed by bolus intravenous and intramuscular administrations. The results were as follows. 1. Concentration of GM in renal cortex was determined in time course after a single administration of 30 minutes intravenous infusion, bolus intravenous and intramuscular injections at a dose of 5 mg/kg. Distribution patterns into renal cortex were almost after these administration routes. Also, no significant difference was found in each time point of cortical concentration among 30 minutes intravenous infusion, bolus intravenous and intramuscular injections. 2. Concentrations of GM in renal cortex and medulla determined at 24 hours after the final administration of 30 minutes intravenous infusion at doses of 3 mg/kg and 30 mg/kg for 10 consecutive days were compared with those obtained by intramuscular administration. Concentration of GM in renal cortex was related to doses, and there was no significant difference between intravenous infusion and intramuscular injection. Concentration of GM in renal medulla was very low compared with that of renal cortex, and there was no significant difference between both administration routes. Histopathological examination of kidney revealed changes of proximal tubular epithelial cells, and there were no differences in the histopathological changes between intravenous infusion and intramuscular injection. 3. Serum concentrations of GM after 30 minutes intravenous infusion were compared with that of intramuscular injection, using the cross-over method. A peaked serum concentration with intravenous infusion occurred immediately after the end of intravenous infusion, whereas that of intramuscular injection occurred 1/2 to 1 hour after injection. Also, there was no significant difference in each time point of serum concentration between both administration routes.
Insights
Gentamicin (GM) administration via intravenous infusion, bolus injection, or intramuscular injection showed similar renal cortex concentrations and nephrotoxicity in rabbits. Serum concentrations peaked faster with IV infusion.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Nephrology
- Toxicology
Context:
- Gentamicin (GM) is an antibiotic commonly administered via various routes.
- Understanding renal accumulation and nephrotoxicity is crucial for safe gentamicin use.
- Comparative studies of different administration methods are needed.
Purpose:
- To compare the renal accumulation, nephrotoxicity, and serum concentrations of gentamicin (GM) following intravenous infusion, bolus intravenous injection, and intramuscular administration in rabbits.
Summary:
- Renal cortex concentrations and histopathological nephrotoxicity were comparable across intravenous infusion, bolus intravenous, and intramuscular gentamicin administration routes in rabbits.
- Dose-dependent gentamicin accumulation was observed in the renal cortex.
- Serum gentamicin concentrations peaked earlier with intravenous infusion compared to intramuscular injection, with no significant differences at other time points.
Impact:
- Provides evidence that intravenous infusion, bolus intravenous, and intramuscular routes result in similar gentamicin distribution in the renal cortex and comparable nephrotoxicity.
- Informs clinical practice regarding gentamicin administration strategies.
- Highlights the importance of monitoring serum concentrations and potential renal effects.
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