INTRODUCTION: The aim of the present work was to examine microdialysis as a technique for the study of pharmacokinetic-pharmacodynamic modeling of antihypertensive drugs. For this purpose, we studied the antihypertensive and the chronotropic effect of @entity1406 and its plasma concentrations in sham operated (SO) and aortic coarctated (ACo) @entity35 at an early @entity101 stage. METHODS: Plasma @entity1406 concentrations were obtained by means of a "shunt" vascular microdialysis probe. Changes in mean arterial pressure and heart rate were also measured in the same experiment. RESULTS: A rapid decay of @entity1406 levels was observed in both experimental groups. For the chronotropic effect, a good association between plasma levels and the chronotropic effect was observed in SO and ACo @entity35 . ACo @entity35 had a greater sensitivity to the chronotropic effect (Emax:-38+/-2%, n=5, p<0.05) than SO animals (Emax:-27+/-1%, n=5). A delay in the blood pressure reduction induced by @entity1406 was observed in both experimental groups. A good association was observed between concentrations of @entity1406 in the effect compartment and the corresponding @entity551 effect in both experimental groups. The calculated PK- @entity1726 parameters were not different between SO and ACo groups. DISCUSSION: A good correlation was found between @entity1406 concentration and its chronotropic and antihypertensive effects in normotensive and ACo @entity101 @entity35 , allowing the employment of PK- @entity1726 models. The microdialysis technique allows simultaneous determination of plasma levels of antihypertensive drugs and their cardiovascular effects, and is therefore a powerful tool for PK- @entity1726 modeling.

Applicability of microdialysis as a technique for pharmacokinetic-pharmacodynamic (PK- XXXX ) modeling of antihypertensive beta-blockers.

@entity101 :: ('MESH:D006973', 'Disease') :: ['hypertensive'] @entity1406 :: ('MESH:D008790', 'Chemical') :: ['metoprolol'] @entity1726 :: ('OMIM:168600', 'Disease') :: ['PD'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity551 :: ('MESH:D007022', 'Disease') :: ['hypotensive']
@entity1726 :: (OMIM:168600,Disease) :: ['PD']
