The relevance of nitrendipine erythrocyte partitioning for the variability of its bioavailability parameters

The pharmacokinetic parameters of nitrendipine were determined in 40 healthy male volunteers and a very high degree of intersubject variability was observed (CV = 39-71%). Since the distribution of nitrendipine to erythrocytes could influence the overall pharmacokinetic variability the correlation between hematocrit and various pharmacokinetic parameters was analyzed, using linear regression. In vitro partitioning of nitrendipine to erythrocytes suspended in physiologic saline was studied over a range of hematocrit and drug concentration values. The correlations of in vivo pharmacokinetic parameters were linear with medium to high correlation coefficients (0.65-0.80). The positive correlation between the volume of distribution and hematocrit and negative between AUC, C(max) and beta parameters indicate that nitrendipine enters and/or is bound to erythrocytes. The results of the in vitro erythrocyte partitioning experiments confirm this observations as the mean values of partition coefficient to erythrocytes was found to be 2.85 +/- 0.17.