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Subarachnoid hemorrhage (SAH) is a devastating type of stroke, leading to high mortality and morbidity rates. Cerebral vasospasm and delayed cerebral ischemia (DCI) are common complications following SAH that contribute significantly to the poor outcomes observed in these patients. Intrathecal (IT) nicardipine delivered via an existing external ventricular drain is an off‐label intervention that has been shown to be correlated with reduced DCI and improved patient outcomes. The current study aims to characterize the population pharmacokinetic (popPK) properties of intermittent IT nicardipine. Following informed consent, serial cerebrospinal fluid (CSF) samples were obtained from 16 SAH patients (50.4 ± 9.3 years old; 13 females) treated with IT nicardipine every 6 h (q6h, n = 8) or every 8 h (q8h, n = 8) for an average of 72 ± 21 doses. High‐performance liquid chromatography was used to quantify CSF concentration from each sample. Our popPK analysis showed that the CSF pharmacokinetics of IT nicardipine in the cohort was adequately described by a two‐compartment model with a lag time. Model parameter estimates were reliable (relative standard error <50%). Intracranial pressure influenced both the total clearance and the central volume of nicardipine (i.e., negative correlation, P <−.001). Calculated PK parameters were similar between q6h and q8h dosing regimens. Despite a small cohort of SAH patients, we successfully developed a popPK model to describe the nicardipine disposition kinetics in the CSF following IT administration. These findings may help inform future clinical trials designed to examine the optimal dosing of IT nicardipine. [ABSTRACT FROM AUTHOR]

This document is a reply to a comment on a previous manuscript regarding the pharmacokinetics of nicardipine in patients with subarachnoid hemorrhage. The authors address some details that were omitted from the original manuscript, such as sample storage and patient outcomes. They explain that the purpose of their study was to determine the pharmacokinetics of nicardipine and that reporting patient outcomes in a small cohort may lead to misinterpretation. They also discuss the relevance of another study and mention the dosing regimen used in a clinical trial. The authors conclude by stating that larger and more rigorously designed studies are needed to develop an optimal dosing strategy for intrathecal nicardipine. [Extracted from the article]