Steady-state serum concentrations of progesterone following continuous intravenous infusion in patients with acute moderate to severe traumatic brain injury.
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 Vd 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.
Wright
David W
DW
Department of Emergency Medicine, Emory University School of Medicine, Emergency Medicine Research Center, 49 Jessie Hill Jr Drive, Atlanta, GA 30303, USA.
Ritchie
James C
JC
Mullins
Richard E
RE
Kellermann
Arthur L
AL
Denson
Donald D
DD
D019540:Area Under Curve; D001930:Brain Injuries / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008657:Metabolic Clearance Rate; D011374:Progesterone / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D012996:Solutions; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
D012996:Solutions; D011374:Progesterone