Blood pressure · 2025
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.
СтатьяСравнительное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Hassan Dimokrat, Peeters Laura E J, Rietdijk Wim J R, van Domburg Bart, Bahmany Soma, Sassen Sebastiaan D T, Hesselink Dennis A, Schinkel Arend F L, Manintveld Olivier C, Galema Tjebbe W, van der Net Jeroen B, Lafeber Melvin, Tumkaya Talip, Koch Birgit C P, Versmissen Jorie
Аннотация
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 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 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 [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.
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 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 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 [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.