Requirements for the documentation of pharmacokinetic properties of antimicrobial agents.

Proper documentation of new antimicrobial drugs for governmental registration authorities includes extensive pharmacokinetic studies. Pharmacokinetics represents the bridge between the in vitro and in vivo phases of drug development. Both healthy human volunteers and patients must be studied, the former during the initial stages of the pharmacokinetic studies. The documentation should give information on the following: absorption from the gastrointestinal tract, bioavailability, pharmacokinetic model, impact of increasing doses (oral and intravenous), metabolism, routes and degree of elimination, interaction with food and other drugs, impact of the steady state, and serum protein binding. Basic pharmacokinetic parameters used are the serum half-life, clearance, distribution volume and dose dependence. The bioavailability of oral doses must be determined using the same dose sizes and subjects. Data on extravascular penetration should also be included in complete documentation. Key diseases in which the pharmacokinetics should be studied are reduced renal and liver function, heart failure, pregnancy, cystic fibrosis and intestinal diseases. The consequences of low age (e.g. newborns) and old age also require some attention.