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Effect of method of administration on extravascular penetration of four antibiotics
Abstract:
The effect of both method of drug administration and serum protein binding on antibiotic penetration into subcutaneous Visking chambers was studied in rabbits. Ampicillin and oxacillin were administered by either repeated intramuscular injection of 30 mg/kg every 4 h or by constant infusion of 7.5 mg/kg per h for 24 h. Gentamicin was given by intramuscular injection of 4 mg/kg every 4 h for 28 h and by constant infusion of 1 mg/kg per h for 24 h. Amikacin was given by intramuscular injection of 8 mg/kg every 4 h for 12 h and by constant intravenous infusion of 2 mg/kg per h for 12 h. Protein binding to rabbit serum was 73% for oxacillin, 9% for ampicillin, 19% for gentamicin, and 0% for amikacin. Chamber concentrations achieved for oxacillin, gentamicin, and amikacin were not significantly different for constant infusion versus intermittent administration. For ampicillin, chamber concentration was slightly higher by constant infusion than by intermittent administration (P less than 0.02). Fluctuations in drug concentration from peak to trough values in the chambers during the intermittent administration studies were markedly dampened when compared with serum fluctuations. This study demonstrates that whereas steady state is reached more rapidly by intermittent administration, the mean steady-state concentration of an antibiotic achieved at an extravascular site is the same or greater by constant infusion than by intermittent dosing. This is true for highly protein bound antibiotics as well as those with low serum protein binding.
Insights
Constant infusion of antibiotics achieves similar or greater extravascular concentrations compared to intermittent dosing, regardless of protein binding. This finding is crucial for optimizing antibiotic therapy and improving patient outcomes.
Area of Science:
- Pharmacokinetics
- Drug Delivery Systems
- Infectious Disease Research
Background:
- Antibiotic penetration into extravascular tissues is critical for infection treatment.
- Understanding the influence of administration methods and protein binding on antibiotic distribution is essential.
Purpose of the Study:
- To investigate the impact of drug administration method (intermittent injection vs. constant infusion) on antibiotic penetration into subcutaneous Visking chambers in rabbits.
- To evaluate the role of serum protein binding in this process for various antibiotics.
Main Methods:
- Antibiotics (ampicillin, oxacillin, gentamicin, amikacin) administered via intramuscular injection or constant intravenous infusion in rabbits.
- Serum protein binding measured for each antibiotic.
- Antibiotic concentrations in subcutaneous Visking chambers and serum analyzed.
Main Results:
- Constant infusion and intermittent administration yielded similar chamber concentrations for oxacillin, gentamicin, and amikacin.
- Ampicillin showed slightly higher chamber concentrations with constant infusion (P < 0.02).
- Intermittent dosing resulted in dampened fluctuations in chamber concentrations compared to serum.
Conclusions:
- Constant infusion provides equivalent or superior mean steady-state antibiotic concentrations at extravascular sites compared to intermittent dosing.
- This holds true for antibiotics with both high and low serum protein binding.
- While intermittent dosing reaches steady state faster, constant infusion may offer more consistent therapeutic levels in tissues.