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Gentamicin distribution in tissues and pleural exudate. A comparison between bolus vs drip-infusion, microbiological
1Department of Pharmacology, University of Padua, Italy.
Abstract:
Concentrations of gentamicin in rat serum and tissues were compared after i.v. (30 mg/kg) bolus injection or continuous infusion. Serum and tissue specimens were collected after 0.5, 1 and 2 h and gentamicin assayed by the microbiological method; serum and pleural exudate samples were also evaluated by enzyme multiplied immunoassay technique (EMIT). Continuous infusion gave higher concentrations of antibiotic in serum after 0.5, 1 and 2 h; in pleural exudate, kidney and muscle after 1 and 2 h from the beginning of administration; the area under the concentration curve (0-2) for serum, pleural exudate and kidney were higher also. These data suggest that continuous infusion may attain the highest serum and tissue levels. Gentamicin concentrations in pleural exudate after both bolus and continuous infusion assayed by the microbiological method, were greater than EMIT. This difference may be explained by the synergistic action between the antibiotic and the pleural exudate.
Insights
Continuous infusion of gentamicin achieved higher serum and tissue concentrations compared to bolus injection in rats. Microbiological assays showed higher gentamicin levels in pleural fluid than EMIT, suggesting a synergistic effect.
Area of Science:
- Pharmacokinetics
- Drug Metabolism and Toxicology
Background:
- Gentamicin is an aminoglycoside antibiotic commonly used to treat bacterial infections.
- Understanding gentamicin's pharmacokinetic profile is crucial for optimizing therapeutic efficacy and minimizing toxicity.
- Intravenous (i.v.) administration routes, including bolus injection and continuous infusion, can significantly impact drug distribution and concentration.
Purpose of the Study:
- To compare gentamicin concentrations in rat serum and various tissues following i.v. bolus injection versus continuous infusion.
- To evaluate the accuracy of microbiological assays versus enzyme multiplied immunoassay technique (EMIT) for gentamicin quantification in serum and pleural exudate.
Main Methods:
- Rats received a single i.v. dose of gentamicin (30 mg/kg) via either bolus injection or continuous infusion.
- Serum and tissue samples (kidney, muscle, pleural exudate) were collected at 0.5, 1, and 2 hours post-administration.
- Gentamicin concentrations were determined using a microbiological assay and EMIT for serum and pleural exudate.
Main Results:
- Continuous infusion resulted in higher gentamicin concentrations in serum at all time points (0.5, 1, and 2 hours).
- Higher gentamicin levels were observed in pleural exudate, kidney, and muscle tissues with continuous infusion at 1 and 2 hours.
- The area under the concentration-time curve (AUC) for serum, pleural exudate, and kidney was greater with continuous infusion.
- Microbiological assays consistently yielded higher gentamicin concentrations in pleural exudate compared to EMIT for both administration methods.
Conclusions:
- Continuous infusion of gentamicin may achieve superior serum and tissue drug levels compared to bolus injection in rats.
- The discrepancy between microbiological and EMIT assays in pleural exudate suggests a potential synergistic interaction between gentamicin and pleural fluid components.
