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

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 (AUC(24h), in mu g/L/24h) and dose corrected (AUC(cor), in mu g/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 Delta BP between blank (pre-perindopril) and nonblank (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 AUC(24h) and AUC(cor) we did not find statistically significant differences between the younger and older group. For perindoprilat AUC(24h), 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 AUC(cor) [15.2, 12.2 - 20.0 and 23.1, 18.5 - 23.5; P = 0.027], respectively. We found a higher but statistically nonsignificant median Systolic BP drop between the blank and nonblank 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, nonsignificant 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 individualized dosing in hypertension management.