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  • Title: Comparative study on acute antihypertensive effects and pharmacokinetics of nisoldipine, nifedipine, nimodipine and nicardipine administered orally to conscious renal hypertensive dogs.
    Author: Takata Y, Kato H.
    Journal: Arzneimittelforschung; 1986 Oct; 36(10):1464-71. PubMed ID: 3814208.
    Abstract:
    The acute antihypertensive effects and pharmacokinetics of orally administered nisoldipine (Bay k 5552) were compared with those of nifedipine, nimodipine and nicardipine in conscious renal hypertensive dogs. The antihypertensive effects of hydralazine were also investigated. Nisoldipine as well as nifedipine, nimodipine and nicardipine dose-dependently lowered mean blood pressure, which was significant 0.5 h and reached its peak effect 1 to 2 h after dosing. Significant antihypertensive effects of hydralazine started 1 h and peaked 3 h after dosing. Of the drugs used, nisoldipine showed the most potent and the longest antihypertensive effects. The fall in mean blood pressure by the drugs was accompanied by a significant increase in heart rate. The tachycardia by nisoldipine and nimodipine, but not by nifedipine and nicardipine, was not dose-dependent. The tachycardia by nisoldipine was not significantly different from those by the other four drugs. The plasma nisoldipine concentration was significantly correlated with the fall in mean blood pressure. This was also the case for nifedipine, nimodipine or nicardipine. However, the slope of the regression line for nisoldipine obtained by plotting the antihypertensive effects against plasma concentrations was greater than those for the other 1,4-dihydropyridines examined. Nisoldipine had the lowest maximum plasma concentration and the longest elimination half-life among the four 1,4-dihydropyridines, resulting in no significant difference in the area under the plasma concentration-time curve. These results suggest that of the drugs examined, nisoldipine is the most potent, has the longest duration of action making it useful for long-term treatment of hypertension.
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