Journal of the neurological sciences · 2025
Impact of cerebral vasospasm therapy on nimodipine exposure in subarachnoid hemorrhage: A population pharmacokinetic study.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Foucher Adrien, Gregoire Matthieu, Dauvergne Jérôme E, Boissier Elodie, Rozec Bertrand, Deslandes Guillaume, Lakhal Karim
Аннотация
BACKGROUND: To prevent delayed cerebral ischemia (DCI) following non-traumatic subarachnoid hemorrhage (SAH), nimodipine is often administered to adults at a fixed dosage, irrespective of potentially influencing clinical factors. This prospective observational study examined whether hemodynamic augmentation (induced arterial hypertension with or without IV-milrinone), used to prevent or treat vasospasm-related DCI, alters nimodipine plasma concentration ([Nimodipine]plasma) - an unexplored pharmacokinetic aspect.
METHODS: Adult patients with SAH receiving IV nimodipine for ≥12 h were prospectively included. Population pharmacokinetic analysis identified covariates influencing [Nimodipine]plasma.
RESULTS: Sixty-one patients were analyzed corresponding to 212 [Nimodipine]plasma measurements: 51 patients (128 measurements) before potential vasospasm and 30 (84 measurements) during hemodynamic augmentation. Creatinine clearance was high and was even higher during hemodynamic augmentation therapy than before potential vasospasm (180 mL/min [IQR:134; 207] vs. 151 mL/min [IQR:120;184], p = 0.02). However, hemodynamic augmentation did not significantly affect total plasma protein level or [Nimodipine]plasma. Only body surface area (BSA), and mean arterial pressure (MAP) were retained as final covariates influencing [Nimodipine]plasma in the final pharmacokinetic model, with BSA exerting a stronger and more consistent effect than MAP. Beyond MAP's own limited effect, hemodynamic augmentation therapy per se had no significant influence on nimodipine clearance.
CONCLUSIONS: Hemodynamic augmentation therapy per se did not significantly affect [Nimodipine]plasma in contrast to patient's BSA, and, to a clinically irrelevant extent, MAP level.
METHODS: Adult patients with SAH receiving IV nimodipine for ≥12 h were prospectively included. Population pharmacokinetic analysis identified covariates influencing [Nimodipine]plasma.
RESULTS: Sixty-one patients were analyzed corresponding to 212 [Nimodipine]plasma measurements: 51 patients (128 measurements) before potential vasospasm and 30 (84 measurements) during hemodynamic augmentation. Creatinine clearance was high and was even higher during hemodynamic augmentation therapy than before potential vasospasm (180 mL/min [IQR:134; 207] vs. 151 mL/min [IQR:120;184], p = 0.02). However, hemodynamic augmentation did not significantly affect total plasma protein level or [Nimodipine]plasma. Only body surface area (BSA), and mean arterial pressure (MAP) were retained as final covariates influencing [Nimodipine]plasma in the final pharmacokinetic model, with BSA exerting a stronger and more consistent effect than MAP. Beyond MAP's own limited effect, hemodynamic augmentation therapy per se had no significant influence on nimodipine clearance.
CONCLUSIONS: Hemodynamic augmentation therapy per se did not significantly affect [Nimodipine]plasma in contrast to patient's BSA, and, to a clinically irrelevant extent, MAP level.