抄録
Therapeutic drug monitoring (TDM) was first introduced for the purpose of controlling the blood concentration of aminoglycoside antimicrobial agents below a toxic level. At present, it is also utilized for monitoring whether or not the blood concentration of a drug administered reaches its therapeutic level. Precise, rapid and simple methods for assaying drug concentration are indispensable for the effective application of TDM. Reliable definition of pharmacokinetics is also important.
Determination of intracorporeal concentration of antimicrobial agents has been achieved by immunoassay (radioimmunoassay and enzyme immunoassay) in addition to conventional bioassay techniques. High performance liquid chromatography is desirable for drugs that produce metabolites in the body. Although the blood level of a drug represents an intra-corporeal concentration, it can also be estimated from the penetration of the drug into the saliva for many drugs. Measurement of drug distribution in tissues and organs is carried out as a common practice using small animals to estimate drug distribution in man. For correct estimation, establishment of a reliable pharmacokinetic model is prerequisite. In studies of pharmacokinetics, due to the advancement and wide-spread use of computers during these last 10 years, a computerized method of calculating pharmacokinetic parameters based on a compartmental model has replaced conventional determination of parameters, including the half-life from graphically arranged data. If reliable parameters are formulated on the basis of amassed data including blood or tissue-drug concentrations through a great many repeated experiments, they will no doubt greatly contribute to the effective application of TDM by appropriate pre-planning of doses to be administered without going through time-consuming pre-TDM calculations. Although methods of pharmacokinetics are already established, a method for accurate estimation of tissue distribution of drugs in man drawn from measurements made in small animals still remains to be established. We have reached a stage of proposing a tentative plan for formulating patterns of a simulation curve for tissuedrug migration in man.
