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Steady‐State Serum Concentrations of Progesterone Following Continuous Intravenous Infusion in Patients With Acute Moderate to Severe Traumatic Brain Injury
Author(s) -
Wright David W.,
Ritchie James C.,
Mullins Richard E.,
Kellermann Arthur L.,
Denson Donald D.
Publication year - 2005
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270005276201
Subject(s) - traumatic brain injury , pharmacokinetics , medicine , neuroprotection , anesthesia , placebo , serum concentration , brain trauma , pathology , alternative medicine , psychiatry
Progesterone (PG) has been shown to provide substantial neuroprotection after traumatic brain injury (TBI) in multiple animal models. As a first step in assessing applicability to humans, the authors examined the effects of acute TBI and extracranial trauma on the pharmacokinetics of PG given by intravenous infusion. Multiple blood samples were obtained from 11 female and 21 male trauma patients receiving PG and 1 female and 3 male patients receiving placebo infusions for 72 hours. Values for C SS , CL, t 1/2 , and V d were obtained using AUC (0–72) and postinfusion blood samples. C SS values were 337 ± 135 ng/mL, which were significantly lower than the target concentration of 450 ± 100 ng/mL. The lower C SS is attributed to the CL, which was higher than anticipated. In addition, t 1/2 was longer and V d was higher than anticipated. These results demonstrate that stable PG concentrations can be rapidly achieved following TBI.