Pharmacokinetic parameters and characteristics relevant to antimicrobial surgical prophylaxis

The penetration of antimicrobial agents to tissues above the minimum inhibitory concentrations of potentially infecting microorganisms is the key to successful prophylaxis after surgery. The levels reach relevant inhibitory concentrations within 10-15 min after therapeutic doses have been administered. This applies even to compounds with a high serum protein binding like flucloxacillin (96% binding). Rapid appearance of extravascular levels is also observed for antibiotics with particularly large molecular size, such as the macrolides. Peak concentrations in extravascular fluid are lower than those in serum. Tissues like the kidneys and liver are exceptions to this general rule because of the special extraction and concentration powers of these key excretory organs. Once the levels in serum and extravascular fluids have equilibrated, extravascular levels tend to be similar to the remainder of the dosage intervals in the case of substances with serum half-life values (t1/2) of 8-12 hours or more (e.g. sulphadiazine, trimethoprim). Compounds with a short t1/2 in the order of ca. 1-2 hours exhibit extravascular concentrations after equilibrium which tend to be above those in serum (e.g. ampicillin, mecillinam). The mechanism of passage from blood to extravascular fluids is by passive diffusion following Fick's law of diffusion. The question remaining is what pharmacokinetic determinants may be relevant to the establishment of extravascular concentrations of antimicrobial agents. The major such variable is the serum concentrations of the agent. A direct linear relationship has thus been observed for a number of substances between the total areas under the concentration versus time curves (AUC) in serum and in peripheral fluids like lymph or tissue chamber fluid.(ABSTRACT TRUNCATED AT 250 WORDS)