1999 Volume 14 Issue supplement Pages 126-127
A novel methods of assessing the extent of bioavailability (EBA) or pharmacological availability (PA) of Arg-vasopressin (AVP), disopyramide (DP) and insulin (INS) from pharmacological data were presented using an integrated pharmacokinetic pharmacodynamic (PK-PD) model. The PK-PD relationship of AVP was influenced by intra-vascular input rate of drug, and the EBA obtained by the anti-diuretic effect following LV bolus study was significantly underestimated. However, good prediction of EBA of DP by QT prolongation of I.V. bolus injection was resulted, because the PK-PD relationship of DP was maintained in the range of dosing rate investigated. Using the relationship between EC50 for hyperglycemic effect and infusion rate of INS, the pharmacological effect of INS could be described by the model. From these results, we concluded that EBA or PA was reasonably predicted by a PK-PD model, provided that appropriate intra-vascular dosing rate as a reference formulation, are available.
