Identifiability of nonlinear compartmental models for plasma protein binding of sulfa drugs

After iv sulfamethoxypyridazine (SMP) or sulfadiazine (SD) 200 and 300 mg/kg in rats,blood levels were assayed and the system parameters were identified with one compartment (two subcompartments) and two compartment models. On the basis of these parameters. the plasma protein binding rates of SMP and SD were calculated and compared with those obtained by the method of equilibrium diajysis in vitro. The calculated plasma protein binding rates within the effective blood concentration ranges were 80-90% for SMP and 50-60 26 for SD. These results were in agreement with those obtained in. vitro and in vivo. With a suitable model, we believe that the calculated plasma protein binding rate reflects the truth in vivo. In this paper. the new calculated methods of nonlinear system identifiability were presented.