PHARMACOLOGICAL PROPERTIES OF CEPHALOSPORINS

The cephalosporins differ in the substituents attached at the 3 and/or 7 positions of the molecule. Very schematically, substitution at C3 mainly modifies the overall pharmacokinetic properties whereas substitution at position 7 influences the antibacterial characteristics. When using the more common "generation" system for classification, three generations can be distinguished on the basis of their antibacterial spectrum, potency, and their stability to beta-lactamases. The first generation cephalosporins have similar antibacterial and pharmacokinetic characteristics. C3-esterfied cephalosporins (e.g. cephalothin and cephapirin) are significantly metabolized. The so-called second generation cephalosporins exhibit only minor differences with respect to the pharmacokinetic properties in contrast to the third generation cephalosporins. The apparent volumes of distribution of most cephalosporins range between seven and 20 1, indicating that they mainly stay in the extracellular space. Plasma protein binding is variable from compound to compound. Generally, the major route of elimination of most cephalosporins is via the kidney except for cefoperazone and ceftriaxone which are both excreted to a large extent by the biliary route. With the exception of cefonicid, cefotetan and ceftriaxone, which have longer elimination half-lives (i.e. 4.5, 3.5 and around eight hours), all other cephalosporins have a half-life ranging from 0.5 to 2.5 hours. The pattern of adverse reactions is comparable for all the cephalosporins although there are slight differences in both the incidence and the type of reactions. The major categories of adverse reactions are gastrointestinal, dermatologic, hypersensitivity, haematologic, hepatic, renal as well as CNS effects. Alcohol intolerance (antabus-like effect) can occur when cephalosporins containing the NMTT moiety are administered concomitantly. Cephalosporins with either a NMTT or a MTD (methylthiadiazole) moiety are linked with hypoprothrombinaemias.