Pharmacokinetics of beta-lactam antibiotics

Beta-lactam antibiotics represent the oldest class of antibiotics used in the treatment of infections. Consequently, a large number of agents have been developed. Penicillins and cephalosporins are generally available for parenteral application. Some are absorbed from the gastrointestinal tract. The serum half-life (t1/2) of most beta-lactams is 1-2 hours. Ceftazidime and temocillin are more long-lasting with a t1/2 of 4-6 hours and ceftriaxone of 8-10 h. These values relate to patients with normal renal function. The elimination is only moderately prolonged for beta-lactams and of little consequences for the dosage regimens, partly because of the high tolerance of this group of antibiotics. Penicillins and cephalosporins are eliminated by glomerular filtration and varying degrees of active transport across the epithelial cells of the renal tubuli and hepatobiliary system. Active transport mechanisms also explain the low concentrations of beta-lactam antibiotics in cerebrospinal fluid. Otherwise, penetration of these agents to unspecialized tissues is good. Substances with a low serum protein binding, such as ampicillin and amoxicillin, reach concentrations in peripheral human lymph which as assessed by the ratios of areas under the concentration curves are 50-80% of the serum levels. The serum protein binding appears to act mainly by inhibiting the rate with which the antibiotic passes into extravascular foci. For instance, temocillin with a serum albumin binding around 85% establishes levels in peripheral lymph which are 50-60% of those in serum. This may be explained by the fact that a higher protein binding is accompanied by more lipid solubility, which are two factors acting in opposite directions as concerns passage by diffusion across body barriers.