Pharmacodynamic model of the haemodynamic effects of pinacidil in normotensive volunteers View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1993-03

AUTHORS

P. Girard, J. L. Saumet, F. Dubois, J. P. Boissel

ABSTRACT

The concentration-effect relationships of pinacidil, a peripheral vasodilator, have been measured in 12 healthy adults who received placebo or pinacidil 25 mg daily for 1 week in a cross-over experiment. Diastolic blood pressure (DBP) and heart rate (HR) were recorded and blood samples were taken on days 1 and 7. Plasma drug concentration-time data were fitted by a biexponential function with zero-order input. The pharmacokinetic model was incorporated into a combined pharmacokinetic-dynamic model (PK-PD) using the Hill equation, which has three parameters: n, the sigmoidicity parameter, Emax the maximum effect and EC50 the concentration which gives 50% of Emax. For ΔDBP, the parameter medians were estimated as n=5, EC50=44.6 ng · ml−1 and Emax=13.5 mm Hg.A hysteresis loop was found when ΔHR was plotted against concentration, which could be fitted by a linear effect compartment model. Simulations showed that experimental ΔDBP points on Day 7 could be predicted from a simulated curve computed by the model using parameters estimated on Day 1.Using the simulation, it was possible to suggest an optimal dosage regimen for pinacidil tablets. More... »

PAGES

177-182

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/bf00315477

DOI

http://dx.doi.org/10.1007/bf00315477

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1041960347

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/8453963


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