Summary
A sensitive HPLC assay has been used to determine the effect of food on plasma endralazine levels in 8 patients with essential hypertension. Subjects were investigated whilst on maintenance therapy with endralazine combined with a fixed antihypertensive baseline treatment for at least 4 weeks, samples being collected after the usual oral morning dose of endralazine (5 mg and 10 mg), on two occasions at least 7 days apart. Endralazine was administered with the concomitant therapy in randomised order once 90 min before and once immediately after a standard breakfast. Acetylator status did not affect its pharmacokinetics in the postprandial study after a 5 mg dose, the peak endralazine concentration averaged 57.5% lower and the AUC had fallen significantly by 49.9%, whereas after 10 mg the postprandial peak level and the AUC were 82.9% and 64.7%, lower. In the 5 mg study the mean arterial blood pressure was decreased by 30 mm Hg in the fasting subjects and by 21 mm Hg in the post-prandial group. For the 10 mg dose the corresponding values were 35 and 24 mm Hg. The blood pressure lowering effect was only weakly correlated with the food — related reduction in the plasma endralazine levels. The results suggest that endralazine has a similar kinetic interaction with food as that found for hydralazine.
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Kindler, J., Rüegg, P.C., Neuray, M. et al. Effect of food intake on plasma levels and antihypertensive response during maintenance therapy with endralazine. Eur J Clin Pharmacol 32, 367–372 (1987). https://doi.org/10.1007/BF00543971
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DOI: https://doi.org/10.1007/BF00543971