The effect of operational stressors on ibuprofen pharmacokinetics.
OBJECTIVE
To determine whether two of the major operational stressors associated with military missions in Afghanistan: dry heat and long durations of soldier patrol (SP), alter the pharmacokinetics of ibuprofen.


METHODS
Thirteen healthy and physically fit participants (19-32 years) were randomized to a four-arm crossover study, as follows: Arm 4 consisted of a simulated 2.5 h SP on a treadmill set at 4.5 km/h, 2% incline (15-min walk/5-min rest cycle) in a climatic chamber set to 42°C, 9% relative humidity. Arm 3 was similar to arm 4 but at room temperature, and arms 1 and 2 were sham SP to 3 and 4, respectively. For the final 2.5 h, participants remained in a semi-supine position. Each participant orally administered one 400-mg Advil Liqui-Gel® capsule. Blood samples were drawn over time and analyzed for (R)-ibuprofen and (S)-plasma ibuprofen concentrations using UPLC/MS/MS. Concentration-time data were analyzed by compartmental methods.


RESULTS
Exercise significantly decreased the t(1/2abs) (h) of (S)-ibuprofen (0.26 to 0.17; p = 0.015) and T(max) (h) for both (R)-ibuprofen (0.97 to 0.73; p = 0.008) and (S)-ibuprofen (1.13 to 0.84; p = 0.005). Values for t(lag) (h) also decreased with exercise for both (R)-ibuprofen (0.38 to 0.22; p = 0.005), and (S)-ibuprofen (0.39 to 0.23; p = 0.001).


CONCLUSIONS
Exercise stress had a significant impact on the absorption profile of (R)- and (S)-ibuprofen. Excessive self-administration rate and dose may not be due to the military operational stressors of heat and soldier presence patrol.
Defence Research and Development Canada Toronto, 1133 Sheppard Ave. West, Toronto, ON M3K 2C9, Canada. Cathy.Boscarino@drdc-rddc.gc.ca
Cathy
C
Boscarino
Andrea N
AN
Edginton
Henry
H
Peng
K Wayne
KW
Riggs
András
A
Szeitz
Bob
B
Cheung
D000328:Adult; D000346:Afghanistan; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D015444:Exercise / Q000502:physiology*; D005260:Female; D006358:Hot Temperature; D006801:Humans; D007052:Ibuprofen / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008889:Military Personnel; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen