Gentamicin intravenous infusion rate: effect on interstitial fluid concentration.

To assess the possible role of intravenous (i.v.) infusion rate as a determinant of degree and rate of interstitial fluid penetration, six rabbits, each with four intraperitoneal implanted capsules, were studied by crossover design after a single dose of 1.7 mg of gentamicin per kg by either slow 2.5-min i.v. bolus or 30 min i.v. infusion. The mean serum peak antibiotic level after slow bolus was 17.4 mug/ml. After 30 min of infusion, mean serum peak was 8.3 mug/ml (P < 0.025). Mean capsule fluid antibiotic levels at 30 min, 1, and 2 h were 0.9 mug/ml, 1.6 mug/ml, and 1.8 mug/ml, respectively, after slow bolus and 0.6 mug/ml, 0.9 mug/ml, and 1.3 mug/ml after 30-min infusion (P < 0.05 at 30 min, P < 0.001 at 1 h, and P < 0.05 at 2 h). Comparison of capsule levels beyond 2 h revealed no significant differences, and peak capsular concentrations achieved by the two methods were similar. Slow 2.5-min i.v. bolus administration of gentamicin established higher interstitial fluid levels during the first 2 h of therapy and may be the preferred mode of delivery when rapid extravascular penetration is desired.