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

The pharmacokinetic parameters of nitrendipine were determined in 40 health y male volunteers and a very high degree of intersubject variability was ob served (CV = 39-71%). Since the distribution of nitrendipine to erythrocyte s could influence the overall pharmacokinetic variability the correlation b etween hematocrit and various pharmacokinetic parameters was analyzed, usin g 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 para meters were linear with medium to high correlation coefficients (0.65-0.80) . The positive correlation between the volume of distribution and hematocri t and negative between AUC, C-max and beta parameters indicate that nitrend ipine enters and/or is bound to erythrocytes. The results of the in vitro e rythrocyte partitioning experiments confirm this observations as the mean v alues of partition coefficient to erythrocytes was found to be 2.85 +/- 0.1 7. (C) 2001 Elsevier Science B.V. All rights reserved.