Differences in antihypertensive drug blood levels in patients with hypertension (DECISION): a prospective study comparing pharmacokinetics and pharmacodynamics of perindopril in younger and older patients

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AIM To investigate age-related differences in the pharmacokinetics (PK) and pharmacodynamics (PD) of perindopril.Methods We compared the PK/PD of perindopril between younger (<50 years) and older (>70 years) participants in a prospective study. The primary outcome was the difference in area under the concentration-time curve (AUC), both dose uncorrected (AUC24h, in µg/L/24h) and dose corrected (AUCcor, in µg/L/24h/mg). We calculated the AUCs of both perindopril and its metabolite perindoprilat. Secondary outcomes included the difference in blood pressure (BP) drop between the two groups, using ΔBP between blank (pre-perindopril) and non-blank (post-perindopril).Results We included 26 participants, of whom 15 (58%) were aged <50 years. The median age in the younger group was 34 years (interquartile range(IQR)=27-41) and 74 in the older group (IQR = 71-77). For both the perindopril AUC24h and AUCcor we did not find statistically significant differences between the younger and older group. For perindoprilat AUC24h, there was a statistically significant difference in the median between the younger [45.8,IQR = 32.0-57.4] and the older group [77.0, 62.5-96.5;p = 0.008], as well as for perindoprilat AUCcor [respectively 15.2, 12.2-20.0 and 23.1, 18.5-23.5;p = 0.027]. We found a higher but statistically non-significant median Systolic BP drop between the blank and non-blank measurements in the older versus younger group (-9 mmHg vs -5 mmHg; p > 0.05).Conclusion Older adults exhibited higher perindoprilat exposure than younger adults, alongside an exploratory, non-significant trend toward greater systolic BP reduction. Given the limited sample size, no causal inference can be drawn from our data; nevertheless, these findings support consideration of age-related factors and individualised dosing in hypertension management.

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