Pharmacokinetic-pharmacodynamic modeling: Why?

At present, pharmacokinetic-pharmacodynamic (PK-PD) modeling has emerged as a major tool in clinical phamacology to optimize drug use by designing rat ional dosage forms and dosage regimes. Quantitative representation of the d ose-concentration-response relationship should provide information for pred iction of the level of response to a certain level of drug dose. Several ma thematical approaches can be used to describe such relationships, depending on the single dose or the steady-state measurements carried out. With conc entration and response data on-phase, basic models such as fixed-effect, li near, log-linear, E-MAX, and sigmoid E-MAX can be sufficient. However, time -variant pharmacodynamic models (effect compartment, acute tolerance, sensi tization, and indirect responses) can be required when kinetics and respons e are out-of-phase. To date, methodologies available for PK-PD analysis bar ely suppose the use of powerful computing resources. Some of these algorith ms are able to generate individual estimates of parameters based on populat ion analysis and Bayesian forecasting. Notwithstanding, attention must be p aid to avoid overinterpreted data from mathematical models, so that reliabi lity and clinical significance of estimated parameters will be valuable whe n underlying physiologic processes (disease, age, gender, etc.) are conside red. (C) 2001 IMSS. Published by Elsevier Science Inc.