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Steady-State Serum Concentrations of Progesterone Following Continuous Intravenous Infusion in Patients With Acute Moderate to Severe Traumatic Brain Injury

From the Departments of Emergency Medicine (Dr Wright, Dr Kellermann), Anesthesiology (Dr Denson), and Pathology and Laboratory Medicine (Dr Ritchie, Dr Mullins), Emory University School of Medicine, Atlanta, Georgia.

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.

Key Words: Traumatic brain injury • pharmacokinetics • continuous infusion • progesterone

Address for reprints: David W. Wright, Department of Emergency Medicine, Emory University School of Medicine, Emergency Medicine Research Center, 49 Jessie Hill Jr Drive, Atlanta, GA 30303.

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