The Effects of Age on the Pharmacokinetics and Pharmacodynamics of Cardiovascular Drugs: Application of Concentration-Effect Modeling. 1. Tolmesoxide.

ABSTRACT

The effects of age on the disposition and hemodynamic responses to the direct acting vasodilator tolmesoxide were examined in an integrated manner using a combined pharmacokinetic--pharmacodynamic (PKPD) modeling approach. Thirty subjects were studied to represent, as far as was possible, an age continuum. Single doses of tolmesoxide (100 mg) and placebo were administered intravenously and blood was withdrawn and heart rate and blood pressure were measured at frequent intervals up to 10 h post dose. No significant effects of age on the disposition of tolmesoxide and its sulfone metabolite were apparent. Tolmesoxide when compared with placebo produced significant changes in blood pressure and heart rate but PKPD modeling failed to demonstrate any significant effects of age on the blood pressure response to tolmesoxide.