Dose-effect analysis pharmacodynamic models

As an example, Hsieh et al. identified toxicodynamic biomarkers in monkey semm that demonstrated a quantitative relationship with drug exposure (Cr iax, AUC) and related pathological events [148], The biomarkers were used for a more precise calculation of the no observed adverse effect level (NOAEL). The safety of three different dosing schedules was predicted using pharmacokinetic pharmacodynamic (PKPD) modeling and biomarker analysis. 

FIGURE 18.16 Theophylline pharmacodynamics in patients with asthma. Effect, which was measured as improvement in forced expiratory volume in 1 second (FEVI), is related to the serum drug level in six patients, who were studied after placebo and tliree incremental doses of theophylline. An Emax model is fit to the concentration-effect data. Based on this analysis, a therapeutic range of 10-20 pg/mL was proposed (shaded area). (Adapted from data published by Mitenko PA, Ogilvie RI. N Engl J Med 1973 289 600-3.)... 

---