Tissue penetration of the fourth generation parenteral cephalosporins.

In this review, the methods employed to study tissue penetration are discussed. Mathematical, animal and human models all have their positive and negative features, however studies in man must be central to studying the pharmacokinetics of these agents. The newly introduced parenteral cephalosporins (cefpirome, cefepime and cefoselis) have been studied in man. In general they penetrate tissues to similar extents to other beta-lactam agents. Non-specialised tissues such as inflammatory exudate and peritoneal fluid are rapidly and extensively penetrated. More specialised tissues (such as prostate) are penetrated to a moderate extent (30 to 50%). Certain sites - such as the CSF - are poorly penetrated (c. 5 to 10%). It is important to have a knowledge of this information prior to therapeutic trials of such agents.