Pharmacokinetics and Food Effect of Enalapril Maleate/Folic Acid Tablets in Healthy Chinese Volunteers: A Phase I, Randomized, Open-label, Single- and Multiple-dose Study

[Speaker] Hengyan Qu:1
[Co-author] Yuanyuan Zhang:1, Zeyuan Liu:1
1:307 Hospital, China

Purpose: To evaluate the pharmacokinetics properties and food effect of enalapril maleate/folic acid tablets after single and multiple-oral dose administration in healthy Chinese volunteers.
Methods: In the single-dose study, 30 subjects were randomized into three groups 1:1:1 to receive enalapril maleate/folic acid tablets: 5 mg/0.4 mg, 10 mg/0.8 mg and 20 mg/1.6 mg respectively. In the multiple-dose study 12 subjects received oral administration of 20 mg/1.6 mg for 10 days. The plasma and urine concentrations of enalapril and enalaprilat were determined using HPLC-MS/MS method.
Results: After administration of a single dose, enalapril wasreaching peak plasma concentrations approximately 1 hr. The mean Cmax value increased in µg/L and mean AUC0-inf values increased from 55.5 to 209.9 µg/L in the range of 5 mg/0.4 mg to 20 mg/1.6 mg dose. Enalaprilat has a longer t1/2 between 7.48 and 9.98 hr than enalapril. Clearance ranged from 30.6 to 35.8 L/h. The accumulative excretion of two drugs dose-dependently increased in urinary excretion. In the fed state the Cmax of enalapril had significantly decreased by 35%. For the metabolite enalaprilat, Cmax had decreased 62% and Tmax had been prolonged by 1.3 hr.
Conclusion:The results suggest that the PK properties of enalapril an enalaprilat are linear with respect to dose. Food consumption could significantly decreased the extent and the rate of absorption of enalapril and the bioavailability of its active metabolite enalaprilat but had no effect on their elimination.
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