Pharmacokinetics and Hemodynamic Effects of Tiapamil: Exercise Performance, Thallium Stress Scintigraphy, and Radionuclide Ventriculography

Abstract

The pharmacokinetic behavior and hemodynamic effects of tiapamil, a calcium antagonist, were studied in 16 cardiac patients during an eight-day treatment course, giving oral doses of 600 mg daily. The hemodynamic effects were investigated using exercise performance tests, thallium stress scintigraphy, and radionuclide ventriculography. The areas under the plasma concentration-time curve after the final dose were greater than after the first dose for both tiapamil (+53 per cent) and its metabolite (+24 per cent). One possible explanation is that tiapamil undergoes saturable intestinal wall metabolism. Alternatively, like verapamil, it may undergo a saturable hepatic elimination process. The hemodynamic test series showed that, despite increasing the exercise tolerance, tiapamil significantly reduced the rate-pressure product, an index of myocardial oxygen requirement. Regional myocardial perfusion clearly improved. Ventriculography showed a significant increase in ejection fraction (+18 per cent), cardiac index (+12 per cent), and stroke volume index (+19 per cent). At the same time, the measured mean arterial pressure decreased significantly by about 10 per cent and the calculated peripheral vascular resistance, by about 19 per cent.

Tiapamil

“…There was no exacerbation of LV dysfunction in five patients with marked impairment of LV performance (EF < 40%) (4). In another study, oral tiapamil (400-600 mg) produced a significant improvement in LVEF (+ 18%) and cardiac output (+ 12%) (12). In patients with ischemic heart disease undergoing cardiac catheterization, intravenous tiapamil produced a fall in TPR, without affecting the heart rate or dLVP/dt,,,, but increasing cardiac output (3,45).…”

“…In patients with liver cirrhosis, the volume of distribution has been shown to increase, leading to a prolonged half-life of tiapamil (28). Following repeated oral administration of tiapamil to patients with ischemic heart disease, there was a significant increase in the area under the plasma concentration-time curve of tiapamil(+53%) and its N-desmethyl metabolite (+24%) when measured following the last dose (12). It has been suggested that, in addition to hepatic biotransformation, tiapamil may undergo saturable intestinal wall metabolism (1237).…”