Effect of method of administration on extravascular penetration of four antibiotics.

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.