The differential time courses of the vasodilator effects of various 1,4-dihydropyridines in isolated human small arteries are correlated to their lipophilicity

Objectives To investigate a possible relationship between the time courses of action of various calcium antagonists and their lipophilicity, character ized as log P-values. Methods The functional experiments were performed in vitro in human small s ubcutaneous arteries (internal diameter 591 +/- 51 mum, n = 7 for each conc entration), obtained from cosmetic surgery (mamma reduction and abdominopla sty). The vessels were investigated in an isometric wire myograph. The vaso dilator effect of the calcium antagonists was quantified by means of log IC 50-values, and the onset of the vasodilator effect for each concentration s tudied was expressed as time to E-eq90-values (time to reach 90% of the max imal effect). Results Log IC50-values were -8.46 +/- 0.09, -8.33 +/- 0.25 end -8.72 +/- 0 .16 for nifedipine, felodipine and (S)-lercanidipine, respectively (not sig nificant). On average, nifedipine reached time to E-eq90 in 11 +/- 1 min. F or felodipine and (S)-lercanidipine the corresponding values were 60 +/- 11 min and 99 +/- 9 min, respectively. The differences between these values we re statistically significant (P < 0.01). In spite of these differences in t he in vitro human vascular model, the three calcium antagonists are equipot ent with regard to their vasodilator effects. Linear regression analysis of the correlation between the logarithm of the membrane partition coefficien t (log P-values) of the calcium antagonists tested [2.50, 4.46 and 6.88 for nifedipine, felodipine and (S)-lercanidipine, respectively] and their resp ective values found for time to E-eq90 was highly significant. Conclusions It appears that a higher log P-value is correlated with a slowe r onset of action. J Hypertens 18:1677-1682 (C) 2000 Lippincott Williams & Wilkins.